The Ebola situation assessment by the WHO published Wednesday suggests that the United Nations (UN)’s apex health body may declare Nigeria and Senegal Ebola-free within days.
This came amid growing acceptance of bitter kola as a possible cure for Ebola as Nigerians have now embraced the local seed for protection against viral infections.
Even Nigerian and United States scientists are beginning to have a second look at the possibilities put forward by Prof. Maurice Iwu.
A presentation of bitter kola seeds, kolaviron, GB-1 as possible post-exposure agents in the management of EVD by Iwu to the National Expert Committee on Ebola, which sat last week to review experimental drugs was greeted with very positive reactions.
Scientists at the review meeting including the Director General of the Nigeria Centre for Disease Control (NCDC), Prof. Abdulsalami Nasidi, Director General of the Nigerian Institute of Industrial Research (NIMR), Yaba, Lagos, Prof. Innocent Ujah, and the Director-General, Nigerian Institute of Pharmaceutical Research and Development (NIPRD), Prof. Karniyus Gamaliel, acknowledged that they had taken to bitter kola.
Indeed, Nigeria through the National Expert Committee on Ebola chaired by Gamaliel and the United States through the U.S. National Institute of Allergy and Infectious Diseases (NIAID), have begun an investigation into the bitter kola cure for EVD.
Already, Bioresources Institute of Nigeria (BION) has signed a non-clinical evaluation/cooperate research agreement with NIAID to investigate valuation compounds submitted by BION for activity against Ebola. The agreement covers pre-clinical and non-clinical tests.
The professor of pharmacy said the proposed project would consist of three related components: Standardised whole seed of Garcinia kola (bitter kola), which is currently available as Garcinia – IHP with the National Agency for Food, Drug Administration and Control (NAFDAC) number No. A7- 1328L; Good Manufacturing Practice (GMP) production of kolaviron for quality evaluation and bioactivity assays using procedure previously described and; preparative Isolation of Garcinia biflavonoids : scaled-up isolation of GB-1 & GB-2 sufficient for under mentioned biological investigations by InterCEDD Laboratories Nsukka.
InterCEDD Laboratories Nsukka and BION are subsidiaries of Bioresources Development Group (BDG) with Iwu as the Executive Director.
Iwu said the scope of work to be undertaken would include pre-clinical bioavailability studies and the determination of the most appropriate mode and route of administration, efficacy studies in non-human primates, human safety determination in phase-one clinical trials, and limited clinical outcome evaluation if approved by relevant clinical committees and agencies.
How does bitter kola protect against Ebola?
Iwu said: “The biflavonoids of the seeds of Garcinia Kola Heckel have shown remarkable broad spectrum antiviral activity in vitro against a variety of viruses including Punta Toro, Pichinde, Sandfly fever, Influenza A, Venezuelan Equine Encephalomyelitis and Ebola, with IC50 values of 7.2-32 μg/ml and MTC of more than 320 μg/ml.
“These biflavonoids have also been shown to possess anti-hepatotoxic, antioxidant, anti-inflammatory and immune enhancing activities in a variety of in vitro and in vivo studies. It is proposed that because Garcinia kola constituents have both antiviral activity and remarkable inhibitory activity against pro-inflammatory cytokines and chemokines, with a long history of safety, that Garcinia biflavonoids should be evaluated for possible use in the early management of human exposure to Ebola virus and/or treatment of the disease, as a means of controlling the massive viral replication and also ameliorate the dysregulated inflammation associated with the onset of the infection.
“Although the pathogenesis of Ebola haemorrhagic fever disease is not well understood, the major clinical features appear to result from intense inflammatory response resembling septic shock.
“Studies in nonhuman primate models have shown that monocytes, macrophages and dendritic cells, the ubiquitous ‘sentinels’ that normally guard the body against microbial invasion, are the major sites of initial viral replication and play the central role in the pathogenesis. The virus is then distributed by circulating monocytes/ macrophages to a wide variety of organs and cell types. The system-wide release of pro-inflammatory cytokines and chemokines by these infected cells causes fever, vascular instability, hypotension and shock, and ultimately multi-organ system failure.
“However, the acute infection of humans with Ebola often results in a paradoxical pattern of immune responses: whereas the early infection is characterised by an outpouring of inflammatory mediators such as interferon (IFN)- α, IFN- β, interleukin (IL)-6, IL-18, MIP-1 α, and MIP-1 β indicating occurrence of pro- inflammatory response. Yet late stage infections are associated with poor immune responses.
“The mechanisms underlying these diverse outcomes are poorly understood. It has been suggested that infection of mononuclear phagocytes is critical, triggering a cascade of events involving cytokines/chemokines and oxygen free radicals. It is the consequence of these events rather than direct viral infection that results in much of the observed pathology.
“Available data also suggest that a strong well regulated innate inflammatory response is associated with a better outcome after EBOV infection. Ebola virus (EBOV, formerly designated Zaire ebolavirus) is one of five known viruses within the genus Ebolavirus.
“It is hereby proposed that Garcinia kola can ameliorate the virus induced suppression of cellular immunity during Ebola virus infection because of its inhibitory effects which involves modulation of multiple signalling of several pro-inflammation pathways/ targets. Kolaviron isolated from Garcinia kola has been shown to interfere with LPS signalling by reducing the activation of several inflammatory transcription factors and that its inhibitory action on IL-6 secretion correlates with inhibition of ERK1/2, p38, Akt, p-c-JUN and JNK signalling pathways; inhibition of dimethyl nitrosamine-induced hepatotoxicity by suppressing COX-2 and iNOS expression: NF-kB and AP-1 as potential molecular targets; protective effects on the neurons of the hippocampus and cerebellum of malnourished mice challenged with the neurotoxin, 3-Nitropropionic acid9; inhibition of tyrosinase10, and reduction of cadmium-induced effects on raw U937 cells and U937-derived macrophages.
“Garcinia biflavonoids also possess strong antioxidant activity which may be useful in protecting the infected cells from the reactive oxygen (ROS)-mediated neuronal cell death associated with Ebola virus infection. There is abundance of literature on the role of oxidative stress in the pathogenesis of viral infections.
Garcinia biflavonoids, Kolaviron belong to a large family of compounds called flavonoids. Flavonoids are interesting compounds that are wide-spread in plants as products of their secondary metabolism and are regularly ingested in small quantities from many edible plants. A propriety product, Garcinia – IHP (NAFDAC No. A7-1328L) has been in pharmacies since 2012.
“Kolaviron and its constituents are unique among flavonoids in that their sub-group, Garcinia biflavonoids (dimeric Eriodictyol) are restricted only to the plant genus Garcinia, and the principal compounds GB-1, GB-2 and kolaflavanone have been found to occur only in the bitter kola, Garcinia kola. Their structures offer significant bioavailability advantages over their monomeric counterparts. A monomeric flavonoid, genistein, a kinase inhibitor has been shown to inhibit Lassa virus and Ebola virus in vitro as a cocktail with tyrphostin.”
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