PRELIMINARY CHEMICAL PROFILING AND ANTIMALARIA STUDIES OF FRACTIONS FROM COMMIPHORA PEDUNCULATA STEM BARK

Contents

 

Table 4.1 Percentage yield of various fractions of extract from Vacuum Liquid Chromatography

 

  

Malaria is a disease transmitted by the microscopic Plasmodium parasite. It is transmitted to humans through the Female Anopheles mosquito (vector). When a female anopheles mosquito carrying the parasite bites a human, the parasite is transmitted into the blood stream and relocates to the liver where they mature and reproduce (Caraballo, 2014). Malaria is a deadly disease. According to data by the United Nations International Children’s Emergency Fund (UNICEF), as of 2021, there were 247 million malaria cases globally that led to 619,000 deaths with 77 percent of these deaths being children below 5 years of age (WHO, 2023).  

After its discovery in the late 1800s, studies took place to find a cure to the disease due to its high mortality rate, especially during World War II. Natural products played a big role in these discoveries. In the early 20th century, the first cure for malaria was discovered from the bark of the Cinchona tree. This was the first effective treatment for malaria. Later, Chloroquine from the Cinchona tree (Cinchona officinalis) and Artemisinin discovered from the sweet wormwood plant were used as cures. Artemisinin is a common component in modern antimalarial drugs. 

Quinine comes from the bark of a tree native to South America. According to legend it was first brought to Europe by a Countess who had been treated with it in Peru in the 1600s. It was introduced in 1632. The bark was named cinchona in 1742 by Linnaeus. In 1820, French chemists isolated quinine from the cinchona bark and quinine became a treatment of reference for intermittent fever throughout the world. Quinine remains an important and effective treatment for malaria today, despite sporadic observations of quinine resistance.

Research by German scientists to discover a substitute for quinine led to the synthesis in 1934 of Resochin (chloroquine) and Sontochin (3-methyl-chloroquine). These compounds belonged to a new class of antimalarials, the four-amino quinolines. The German research went no further and the formula for Resochin was passed to a US company. American researchers made slight adjustments to the captured drug to enhance its efficacy. The new formulation was called chloroquine. Only after comparing chloroquine to the older and supposedly toxic Resochin, did they realize that the two chemical compounds were identical.

Following the war, chloroquine and DDT emerged as the two principal weapons in WHO’s global eradication malaria campaign. Subsequently, chloroquine resistant P. falciparum probably arose in four separate locations starting with the Thai-Cambodian border around 1957; in Venezuela and parts of Colombia around 1960; in Papua New Guinea in the mid-1970s and in Africa starting in 1978 in Kenya and Tanzania and spreading by 1983 to Sudan, Uganda, Zambia and Malawi.

Since then, various other antimalarial drugs were discovered including; Sulfadoxin, Mefloquine, Artemisinin. Sulfadoxin emerged from the anti-malarial pipe line during World War II. It was gotten from a Pyrimidine derivative, Proguanil. This led to further study of its chemical class and the development of Pyrimethamine. Mefloquine’s efficacy in preventing falciparum malaria when taken regularly was shown in 1974 and its potential as a successful treatment agent was shown soon after. Resistance to Mefloquine began to appear in Asia in 1985, around the time the drug became generally available. Artemisinin was isolated by Chinese scientists in 1972 from Artemisia annua (sweet wormwood), better known to Chinese herbalists for more than 2000 years as Qinghao. Artemisinin has been a very potent and effective antimalarial drug, especially when used in combination with other malaria medicines. Combining an Artemisinin drug with a partner drug that has a longer half-life was found to improve the efficacy of the Artemisinin. It also reduced treatment duration with the Artemisinin and appeared to reduce the likelihood of development of resistance to the partner drug (History of antimalarial drugs, 2023)

Commiphora pedunculata is a natural product of anti-malarial importance. It is from the family Burseraceae. It is an angiosperm. C. pedunculata is a savannah shrub of about 4 – 6m height but may sometimes grow to between 12 and 15m. The bark of most C. pedunculata is papery and peels off into papery flakes, revealing a green bark underneath. The leaves are mostly compound. The fruit of C. pedunculata greatly enhances the identification of the specie. When ripe, the fruit splits into halves revealing a brightly colored pseudo-aril. This fleshy appendage completely or partially encompasses the seed as part of an attachment around part of the seed. The shape of the pseudo-aril differs from species to species. The flowers may be uni or bisexual, with the unisexual flowers only being semi developed with non-functional stamens (Steyn, 2003). 

Commiphora pedunculata stem bark has been reported to treat infected wound, the root is usually chewed for treating cough and it is also used for treating jaundice, nausea and yellow fever, the decoction of the leaves and stem bark is used for the treatment of dysentery and diarrhea. In Nigeria, the common names of C. pedunculata are Luban (Arabic) and Daashin jeji (Hausa). 

 

Figure 1: Commiphora pedunculata plant

Since their discovery, antimalarial drugs such as chloroquine have been administered as a cure to sick patients. However, over recent years, it has been discovered that malaria parasites have begun gaining resistance to these drugs. This poses a threat to humanity. According to WHO malaria killed 619,000 people in 2021, making it important to discover effective antimalarial drugs (WHO, 2023).

Drug resistance has been observed in two out of four malaria parasites (Plasmodium falciparum and P. vivax). Plasmodium falciparum has developed resistance to anti-malarial drugs such as Chloroquine, Quinine, Sulfadoxin and Mefloquine. This has resulted in an urgent need to find new malaria drugs from new sources. 

The aim of the experiment is to identify the compounds present in Commiphora pedunculata and to determine the anti-plasmodial properties of Commiphora pedunculata in a mouse model of malaria.