From Herbs to Drugs: Inaugural lecture by Professor Ibrahim Iliya

From Herbs to Drugs: Natural Product a Potential Source of Bioactive Compounds – Professor Ibrahim Iliya

Ibrahim Iliya is a Professor of Natural Product and Pharmaceutical Chemistry in the Faculty of Pharmacy, University of Maiduguri. Professor Iliya delivered his inaugural lecture which is the 76^th of the University of Maiduguri lecture series on the 30^th of May, 2019 were he stressed the importance of natural products as source of bioactive compounds.

Professor Ibrahim Iliya said several chemical substances have been produced by nature and used for medicinal purposes, dietary supplements, flavoring agents and spices, agricultural pesticides and herbicides. In addition, they provide clues of taxonomical importance to animals and plants.

He defined natural product as a chemical substance produced by living things or found in nature that possesses pharmacological or biological activity. The Professor described his area of research as a multidisciplinary course that relates to many of the science courses such as molecular and cellular biology, synthetic and analytical chemistry, biochemistry, biotechnology, pharmaceutical sciences, taxonomy, microbiology, agriculture, proteomics, genomics and metabolomics.

In the course of his lecture, Professor Iliya described the important role played by natural products for thousands of years in health care system. He cited examples of ancient civilizations such as the Sumerian, Egyptian, Ayurveda, Unani, European, Chinese, and the Mediterranean culture who had used natural products as medicines for thousands of years.

He classified main sources of drugs as three, namely the serendipity which include luck and observation of side effect; natural sources which is made of plants, animals, mineral sources and structured investigation (focus or random studies). He went on to highlight how drugs such as penicillin and anticoagulants (coumarins) were found by luck and minoxidal (hair growing cream) acetyl salicylic acid-aspirin (antiplatelet aggregation) and senidifil (viagra) were found by observation of side effects.

He also gave a briefed on how drugs such as captopril (antihypertensive agent), conjugated oestrogen (used for menopausal syndrome) and insulin were obtained from animals. Captopril is a drug from Brazilian Pit Viper venom. The venom kills by lowering the blood pressure to zero level by inhibiting the action of angiotensin converting enzyme which regulates the BP and subsequently led to the understanding of the ACE in BP. Another example of drugs from animal is the urine of  pregnant horse which was found to be rich in oestrogen and used in the treatment of menopausal syndromes.

The lecturer has studied many plant species however and in his inauguaral lecturer he presented the stilbenoids in the families of Gnetaceae and Welwitschiaceae. He carried his audience through a phytochemical studies on the stilbenoids constituents of five species of Gnetum namely G. africanum, G. gnemon, G, gnemonoides, G. latifolium and G. parvifolium, which he said resulted in the isolation of sixty eight stilbene derivatives, amongst which forty-four were new compounds and in the phytochemical studies of the methanol extract of the stem and root of a cultivated Wilwitchia mirabilis reported the isolation of twenty one stilbeniod among which were twelve new compounds. The two families are classified in the plant Order of Gnatales but there are controversies on their classification.

The compounds were isolated from the plants using opened column chromatography with silica gel, sephadex LH-20 and ODS as absorbents and the structures of the isolated compounds were determined using Nuclear Magnetic Resoance Spectrocopy (1H-NMR, 13C-NMR, Dif-NOE, NOESY, H-H COSY, HMQC, HMBC), Masss Spectroscopy (EI-MS, FAB-MS etc) and Optical Rotation Spectroscopy.

The new compounds in the two families are flavonostilbenes, stilbene glucosides, stilbene dihydroderivatives and stilbene oligomers. The flavonostilbenes are novel compounds that were formed by the oxidative coupling of a stilbene monomer (resveratrol, oxyresveratrol and piceatannol unit) with a flavan-3-ol unit. The occurrence of flavonostilbene has been reported in some species of Leguminosae where stilbene unit is coupled with flavanone unit. This is first report of the isolation of flavonol with a stilbene. The isolation of oligomeric stilbene glucosides and dihydroderivative (compound in which olefinic moiety is been replaced by an alkane group) are also rare in nature, but they were distributed abundantly in the families of Gnetaceae and Welwitschiaceae and therefore are phytochemically important in the phylogenetic relationship between Gnetum and Welwitschia.

The oxidative coupling of stilbene monomers in Gnetum and Welwitschia are different from other stilbene oligomers in other families (Cyperaceae, Dipterocarpaceae, Leguminosae and Vitaceae) were homogeny coupling of resveratrol units is involved. In Gnetum and Welwitschia species, coupling is heterogenic where several stilbene monomers (oxyresveratrol, isorhapontigenin ana piceatannol) in addition to resveratrol units are involved. Two of the compounds were the first tetrameric stilbenes to be isolated from the family of Gnetaceae. Finally, the isolation of compounds such as gnetin C, E and I, and dihydrostilbene, in addition to glucosides in the two families is of chemotaxonomical importance in study of the morphological relationship of Gnetaceae and Welwitchiaceae families.

He went on to explained that they have screened some of the plant extracts and pure compounds for maillard reaction inhibition and prevention of diabetes complications (advance glycation end products, AGE), anticancer (apoptosis), anti-HIV/AIDS (TZM bl assay), melanogenesis (skin lightening) and anti-oxidants activities.

He said in their search for an extract with AGEs inhibitory activity, they found the acetone extract of stem lianas of G. parvifolium showed a strong inhibitory action of 79% in maillard reaction at 10 mg/ml. Further investigation of the extract led to the isolation of 2b-hydroxy amphelopsin F which exhibit a potenty of 70% at concentration of 10 mg/ml in Maillard reaction.

Fifty six pure stibenoids were screened for cytoxicity against HL 60, SW 480, U 937 and PC 3. Six of the compounds wiped out the cells at conc. of 10mM. Further experiments showed that two of the compounds gnemonol G and gnetin I induced activities with an IC₅₀ of 12.2 and 10.5mM respectively. The nuclear condensation and fragmentation, and DNA ladder formation observed when HL-60 cells were treated with the two compounds revealed that the two compound induced growth suppression by apoptosis. The result of the study also revealed that catechol units in stilbenoids are required for cancer activity, whereas weak activities were observed in compounds with dihydroderivatives and glycosides in their structures.

The results of the HIV infectivity assay conducted on eight plants (8) roots, leaves and roots previously identified to have suppression of HIV/AIDS viruses on 3B and JR-CSF viruses using TZM Bl assay showed eight plants with various degrees of activities and among the plants, Plant 1A showed the most activity with 90% inhibition of the two viruses. Further chromatographic and spectroscopic analysis of plant 1A led to the isolation of quercetin, b-sitosterol, epicatechin, lupeol and stigmasterol. The activity of the extract might be attributed to the ability of the extract to kill the viruses or strengthen the ability of the cells to fight the virus.

In the melanogenesis assay conducted on some of the extracts revealed some extracts showing varied degrees of potencies. The bioassay guided fractionation of the two most potent extract (G. gnemon and G. africanum led to the isolation of gnetol, a compound commonly found in  the Genus of Gnetaceae exhibited strong inhibitory activity against tyrosinase activity. It suppressed melanin biosynthesis with an IC₅₀ of 4.5mM and complete inhibition was observed at 25mM. The IC₅₀ was found to be stronger than the standard, Koji acid which has an IC₅₀ of 139mM.

The antioxidant activities of some the isolates were also conducted in lipid peroxide inhibition and scavenging activity for super oxide in xanthine-xanthine oxidase were also investigated. In addition, the DPPH radical scavenging activities. Most of the compounds exhibited considerable activities in all the assays conducted.

In conclusion he explained that for a stilbenoid to have anticancer and antioxidant activity it must possess a catechol unit, the larger the number catechol units the greater the activity. It was also observed that stilbenoids containing sugar exhibits lower anticancer and antioxidant activities.

Finally, Professor Iliya highlighted the importance of functional food to health. These are foods which in addition to their nutritional values have medicinal uses. An example of such food is the Adansonia digitata (Kuka in Hausa). The vegetable contains phenolic compounds such as rutin, rutinoside and catechin which are known to reduce oxidative stress, prevent aging and neuro-degenerative diseases. Other examples include millet, soya beans tiger nuts, ground nuts etc. He therefore encouraged the use of functional food for healthy life.