EXECUTIVE SUMMARY
Title
The Potential Use of Bitter Leaf (Vernonia amygdalina) in Coronavirus Disease (COVID-19)
Objective
The objective of this report is to assess current available evidence on the potential of bitter leaf (Vernonia amygdalina) in COVID-19 management based on the following:
- Efficacy: focusing on bitter leaf reported properties of (1) antiviral, (2) modulation of immune response including anti-inflammatory, and (3) role as other supportive therapy or management of COVID-19; and their respective potential mechanism(s) of actions.
- Safety of bitter leaf
Methodology
Electronic databases were searched using pre-determined terminologies such as ‘vernonia amygdalina’, ‘antiviral’, immunomodulatory’, ‘immune response’, ‘inflammation’, ‘mechanism of action’, and ‘safety’. All clinical and preclinical studies (both in vitro and in vivo) related to safety and efficacy or effectiveness of bitter leaf in treating viral diseases were included.
Results and discussion:
- There are no documented direct antiviral effects of Vernonia amygdalina. In a clinical study, V. amygdalina aqueous leaf extract given together with antiretroviral drugs demonstrated immune enhancing effects of increasing CD4+ cell counts.
- The V. amygdalina demonstrated differential and contrasting anti-inflammatory and immune enhancing effects in several preclinical studies of different inflammatory models such as bacterial infection, diabetes, and joint inflammation.
- Synergism between chloroquine and V. amygdalina has been reported for malaria but there are still no documented benefits of this combination for treatment of COVID-19 or any viral and respiratory infection.
- In terms of safety, V. amygdalina leaf extract is generally safe as aqueous and acetone extract but caution should be practiced in ethanol extracts as toxicity has been reported on testicular toxicity at 300 mg and 600 mg/kg and another paper showed low LD50 of 289 mg/kg compared to aqueous extract (LD50 > 5,000 mg/kg).
Conclusion
Bitter leaf (Vernonia amygdalina) demonstrated differential and contrasting anti-inflammatory and immune enhancing effects in several preclinical studies of different inflammatory models, such as bacterial infection, diabetes, and joint inflammation. There is no evidence of direct antiviral properties. In humans, given together with antiretroviral drugs, a single study demonstrated immune enhancing effects of V. amygdalina aqueous leaf extract in increasing CD4+ cell counts. It is important to identify the single and combination of various bioactive compounds found in V. amygdalina that may contribute towards reported differential anti-inflammatory (e.g. reduction of IL-6) and immune enhancing effects (as adjunct to vaccination), before further investigating their potential to be applied specifically in COVID-19 management.
Even though synergism between chloroquine and V. amygdalina has been reported for malaria, at present, there are still no documented benefits of this combination for treatment of COVID-19 or any viral and respiratory infection. Potential of synergism may be explored in future investigations, keeping in mind that as the combination may potentiate efficacy, it may also increase toxicity. Toxicology studies on the specific combination formula is essential.
Although consumption of V. amygdalina is generally considered to be safe in humans, additional safety considerations should be given on the type of extract used as ethanol extract has shown toxicity at 300 and 600 mg/kg in animal studies.
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