THE LACK OF QUALITY CONTROL AND SCIENTIFIC EVIDENCE FOR THE EFFICACY AND SAFETY OF MEDICINAL PLANTS

CHAPTER ONE

INTRODUCTION AND LITERATURE REVIEWINTRODUCTION

Albumin, globulin, total protein, body weight and glucose are blood tests that gives information about the state of an individual’s liver. Albumins are associated with functionality. These tests can be useful in the evaluation and management of patients with hepatic dysfunction. They can be used to detect the presence of liver disease, gauge the extent of known liver damage and follow the response to treatment.

Medicinal plants have been the main stay of traditional herbal medicine amongst rural dwellersworld-wide since antiquity to date. The therapeutic use of plants certainly goes back to the Sumerian and the Acadians civilization is about the third millennium BC. Hippocrates (ca. 460-377 BC), one of the ancient authors who described medicinal natural products of plants and animal origins, listed approximately 400 different plant species for medicinal purposes (Taylor et al., 2001).

Medicinal plants are plants which contain substance that could be used for therapeutic purposes or which are precursors for the synthesis of useful drugs (Abolaji et al., 2007). Medicinal plants, since time immemorial have been in virtually all cultures as a source of medicine. Over 5,000 plants are known to be used for medicinal purposes in Africa but only a few have been described for study (Taylor et al., 2001).

Recently, concerns have been raised over the lack of quality control and scientific evidence for the efficacy and safety of medicinal plants. Medicinal plants typically contain several pharmacological active compounds that may act individually, additively or in synergy to improve health (Azaizeh et al., 2003).

1.1.LITERATURE REVIEW

1.1.1. ALBUMIN

The albumins (formed from Latin: albumen) (Haefliger et al., 1989) are a family of globular proteins, the most common of which is serum albumin. The albumin family consists of all proteins that are water-soluble, are moderately soluble in concentrated salt solutions, and experience heat denaturation. Albumins are commonly found in blood plasma, and are unique from other blood proteins in that they are not glycosylated.

Albumin is a protein made specifically by the liver, and can be measured cheaply and easily. It is the main constituent of total protein (the remaining from globulins). Albumin levels are decreased in chronic liver disease, such as cirrhosis. It is also decreased in nephritic syndrome, where it is lost through the urine. The consequence of low albumin can be edema since the intravascular oncotic pressure becomes lower than the extra vascular space. Reference range 3.5 to 5.5g/dl.(Sugio et al., 1999).

FUNCTION

Serum albumin is the main protein of human blood plasma (Mayer et al., 1994). It binds water, cations (such as Ca2+, Na+ and K+), fatty acids, hormones, bilirubin, thyroxine (T4) and pharmaceuticals (including barbiturates) - its main function is to regulate the colloidal osmotic pressure of blood. 

TYPES

Serum Albumin

Serum albumin is the most abundant blood plasma protein and is produced in the liver and forms a large proportion of all plasma protein. The human version is human serum albumin, and it normally constitutes about 50% of human plasma protein (Mayer et al., 1994).

Serum albumins are important in regulating blood volume by maintaining the oncotic pressure (also known as colloid osmotic pressure) of the blood compartment (Mayer et al., 1994).

They also serve as carriers for molecules of low water solubility this way isolating their hydrophobic nature, including lipid soluble hormones, bile salts, unconjugated bilirubin, free fatty acids (apoprotein), calcium, ions (transferrin), and some drugs like warfarin, phenobutazone, clofibrate & phenytoin. For this reason, it's sometimes referred as a molecular "taxi". Competition between drugs for albumin binding sites may cause drug interaction by increasing the free fraction of one of the drugs, thereby affecting potency (Gaull et al., 1984).

SPECIFIC TYPES INCLUDE:

Human Serum Albumin

Low albumin (hypoalbuminemia) may be caused by liver disease, nephrotic syndrome, burns, protein-losing enteropathy, malabsorption, malnutrition, late pregnancy, artefact, genetic variations and malignancy.

High albumin (hyperalbuminemia) is almost always caused by dehydration. In some cases of retinol (Vitamin A) deficiency, the albumin level can be elevated to high-normal values (e.g., 4.9 g/dL). This is because retinol causes cells to swell with water (this is also the reason too much Vitamin A is toxic) (Gaull et al., 1984). 

Normal range of human serum albumin in adults (> 3 y.o.) is 3.5 to 5 g/dL. For children less than three years of age, the normal range is broader, 2.9-5.5 g/dL (Alderson and Bunn, 2011).

MEDICAL USES

For patients with low blood volume, there is no evidence that albumin reduces mortality when compared with cheaper alternatives such as normal saline, or that albumin reduces mortality in patients with burns and low albumin levels. Therefore, the Cochrane Collaboration recommends that it not be used, except in clinical trials (Alderson and Bunn, 2011). 

Albumin is a protein made by the liver. A serum albumin test measures the amount of this protein in the clear liquid portion of the blood.

This test can help determine if a patient has liver disease or kidney disease, or if the body is not absorbing enough protein.

Albumin helps move many small molecules through the blood, including bilirubin, calcium, progesterone, and medications. It plays an important role in keeping the fluid from the blood from leaking out into the tissues.

The normal range is 3.4 - 5.4 grams per deciliter (g/dL) (Berk and Korenblat, 2011)

Lower-than-normal levels of serum albumin may be a sign of:

Kidney diseases

Liver disease (for example, hepatitis, or cirrhosis that make cause ascites)

Decreased blood albumin levels may occur when your body does not get or absorb enough nutrients, such as:

After weight-loss surgery

Crohn's disease

Low-protein diets

SprueWhipple's disease

Increased blood albumin level may be due to:

Dehydration

High protein diet (Pratt, 2010)

1.1.2. BODY WEIGHT

Underweight, normal, overweight, and obese are all labels for ranges of weight. Obese and overweight mean that your weight is greater than it should be for your health. Underweight means that it is lower than it should be health. Healthy body weight depends on sex and height. For children, it also depends on age (Pai et al., 2000).A sudden, unexpected change in weight can be a sign of a medical problem. Causes for sudden weight loss can include

Thyroid problems

Cancer

Infectious diseases

Digestive diseases

Certain medicines

Sudden weight gain can be due to medicines, thyroid problems, heart failure, and kidney disease.The term body weight refer to a person's mass or weight (Walpole et al., 2012). Body weight is measured in kilograms, a measure of mass, throughout the world. Excess or reduced body weight is regarded as an indicator of determining a person's health, with body volume measurement providing an extra dimension by calculating the distribution of body weight (Lubitz et al., 1988).

TOTAL PROTEIN

The total protein test measures the total amount of two classes of proteins found in the fluid portion of blood. These are albumin and globulin (Landry and Bazari, 2011).

Proteins are important parts of all cells and tissues.

Albumin helps prevent fluid from leaking out of blood vessels.

Globulins are an important part of the immune system.

The normal range of total protein is 6.0 to 8.3 gm/dL (grams per deciliter) (Klein, 2011).

GLUCOSE

Glucose is a carbohydrate, and is the most important simple sugar in human metabolism. Glucose is called a simple sugar or a monosaccharide because it is one of the smallest units which has the characteristics of this class of carbohydrates. Glucose is also sometimes called dextrose. It is one of the primary molecules which serve as energy sources for plants and animals. It is found in the sap of plants, and is found in the human bloodstream where it is referred to as "blood sugar". The normal concentration of glucose in the blood is about 0.1%, but it becomes much higher in persons suffering from diabetes.

Glucose is manufactured by plants with the aid of energy from the sun in the process called photosynthesis. This synthesis is carried out in the small energy factories called chloroplasts in plant leaves. The chloroplasts capture the energy from light and fabricate glucose molecules from carbon dioxide from the air and water from the soil.

BIOSYNTHESIS

In plants and some prokaryotes, glucose is a product of photosynthesis. In animals and fungi, glucose results from the breakdown of glycogen, a process known as glycogenolysis. In plants the breakdown substrate is starch.

In animals, glucose is synthesized in the liver and kidneys from non-carbohydrate intermediates, such as pyruvate, lactate and glycerol, by a process known as gluconeogenesis.

COMMERCIAL

Glucose is produced commercially via the enzymatic hydrolysis of starch. Many crops can be used as the source of starch. Maize, rice, wheat and cassava are all used in various parts of the world. Most commercial glucose occurs as a component of invert sugar, a roughly 1:1 mixture of glucose and fructose. Glucose has approximately 75 % the sweetness of sucrose (table sugar) (Mc Murry and John, 2012).

SOURCES AND ABSORPTION

Most dietary carbohydrates contain glucose, either as their only building block (starch and glycogen), or together with another monosaccharide( sucrose and lactose) (Ferraris and Ronaldo, 2001).

In the lumen of the duodenum and small intestine, the glucose oligo- and polysaccharides are broken down to monosaccharides by the pancreatic and intestinal glycosidases. Other polysaccharides cannot be processed by the human intestine and require assistance by intestinal flora if they are to be broken down; the most notable exceptions are sucrose (fructose-glucose) and lactose (galactose-glucose). 

Liver cell glycogen can be converted to glucose and returned to the blood when insulin is low or absent; muscle cell glycogen is not returned to the blood because of a lack of enzymes. In fat cells, glucose is used to power reactions that synthesize some fat types and have other purposes. 

Glycogen is the body's "glucose energy storage" mechanism, because it is much more "space efficient" and less reactive than glucose itself (Ferraris and Ronaldo, 2001) .IN HYPOGLYCEMIA MANAGEMENT

Individuals with diabetes or other conditions where hypoglycemia (low blood sugar) may occur often carry small amounts of sugar in various forms. One sugar commonly used is glucose, often in the form of glucose tablets (American Diabetes Association, 2010).

HIPPOCRATEA WELWISTCHII

Hippocratea welwitschii oliv is a plant found in the tropical area of West Africa. It is said by tradomedicine to be effective in the treatment of malaria, epilepsy and diabetes. Those from the rural area also use it as chewing stick and traditional herb. Also, women found in Ibibio (calabar) use it as fattening agent.

The root has been used by the natives of Akwa Ibom state for the treatment of epilepsy. Phytochemical tests on the powdered root sample using standard method of analysis showed that it contained saponins, alkaloids, phenols and glycosides.

The (saponins) compounds serve as natural antibiotics, which help the body to fight fungal infections, combact microbes and viruses and knock out some tumor cells, particularly lung and blood cancers (Barakat et al., 1993). They also bind blood cholesterol, thereby reducing heart problems but the most exciting and outstanding prospect for saponins are how it inhibit and kill cancer cells.

1.2.1. DESCRIPTION 

Climber of closed primary or mature secondary forest, or in thickets of secondary scrubs, wholly glaborous. Leaves are sub-membranous or length coriaceous, broadly elliptical or obovate, rather obtusely cuspidate or shortly acuminate, reticulation scarcely prominent, 2-4 inches long.

1.2.2. CLASSIFICATION

Kingdom: Plantae.

Phylum: Magnoliophyta.

Class: Magnoliopsida.

Order: Celastrales (49).

Family: Celastraceae (440).

Genius: Hippocratea (32,510).

Species: Hippocratea welwitscii (539,756).

1.2.3.COMMON NAMES LANGUAGE AND ORIGIN

Bittersweet family English

Manogiegbini Liberia

Adangmeakladofi Ghana

Ijan Yoruba

Nyaworo uru ambombo Efik and Ibibio

SYNONYM: simicratea welwitschii oliv1.2.4.GEOGRAPHICAL DISTRIBUTION

The plant is commonly found in areas like: Angola, Cameroon, Congo, Gabon, Tanzania, Uganda, Togo, Guinea, Benin, Ivory Coast and Nigeria.

1.2.4. PHYTOCHEMICAL ANALYSIS

The phytochemical analysis showed that the root of H. welwitschii contains saponins, alkaloids, phenols, terpenoids and glycosides in varying amounts 1.66 x 10-2, 3.67 x 10-3, 2.64 x 10-2, 3.08 x10-2 and 2.01 x 10-2 ug/g respectively, minerals like K, Na, Cr, Ca, Mg, Cu, Mn, Fe, Pb, Zn, Cd, Co, Ni and Se(Poornima and Ravishankar, 2009).

1.2.5. ECONOMIC IMPORTANCE OF HIPPOCRATEA WELWITSCHII

Its phytochemical contents have attributed a great importance to the use of the plant in treatment of various diseases, the presence of saponins helps in binding blood cholesterol, thereby reducing heart problems but the most exciting and outstanding prospect for saponins are how they inhibit and kill cancer cells (Poornima and Ravishankar, 2009). It has also been reported that they do so without destroying normal cells on the process, as is the mode of some cancer fighting drugs (Ryam and Shattuk, 1994; Poornima and Ravishankar, 2009). Since cancer cells have more cholesterol and thus interfere with cell growth and division (Ryam and Shattuck, 1994; Poornima and Ravishankar, 2009). Some plant extracts containing some alkaloids (dihydrodioscorine) have been reported to possess a long lasting hypotension and contraction of the smooth muscle fibres in the intestine both in-vivo and in-vitro when administered to animals (Poornima and Ravishankar, 2009).

The presence of phenols, saponins and alkaloids in the root sample could confer antibiotic and hypoglycemic property on the plant (Jacob and Burri, 1996). Phenol, saponins and alkaloids in the root of the plant are responsible for its use in the treatment of cough, dyssentry, inflammations and ringworm (Frankel et al., 1993; Jacob and Burri,1996). 

The mineral composition of the root of H. welwitschii are known to play important metabolic and physiological roles in living system (Ujowundu et al., 2010). Iron, Zinc, Selenium and Manganese strengthen the immune system as antioxidants , while magnesium, zinc, selenium are also known to prevent cardiomyopathy, muscle degeneration, growth retardation, alopecia, dermatitis, immunologic dysfunction, gonadal atrophy, impaired spermatogenesis, congenital malformations and bleeding disorders (Ujowundu et al., 2010). 

1.2.6. LOCAL USE

Some traditional healers claimed that the root of the plant is used in the treatment of Malaria, Typhoid fever and Obesity. It was also claimed to stimulate menstruation (bark of the root), lower blood pressure, and used as a general body (internal) cleansing agent. It is prepared by boiling the bark of the root and taken as a drink or grinded into powdered form and taken with palpable food such as palp (akamu) or taken with tea without milk or sugar. Side effects only result when the extract is taken in excess, the common side effects are: drownsiness, dysentery and weakness of the body. However, it has not been shown if it can cure diabetes.

1.2.7. DIABETES MELLITUS

Diabetes mellitus is a chronic metabolic disorder of carbohydrate, proteins and fat due to absolute or relative difficiency of insulin deficiency of insulin secretion with/without varying degree of insulin resistance. It is characterized by hyperglycemia, dyslipidemia, and protein metabolism that could lead to morbidity and mortality.

None of the antidiabetic drugs could give a long term glycemic control without causing any adverse side effects. Meanyle, medicinal plants that are effective in controlling plasma glucose level with minimal side effects are commonly used in under developed countries as an alternative therapy. In Africa, hundreds of plants are used traditionally for the management and/ or control of diabetes mellitus. Unfortunately, only a few of such medicinal plants have been scientifically validated.