Prof. John Kenneth Mensah

Senior Lecturer

Dept: Chemistry
Chemistry Department
Private Mail Bag
Kumasi, Ghana

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Research Areas/Interests

Bio-organic Chemistry where research interest is at the intersection of chemistry with biology....~more

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Herbal Medicine 3/4

Few Facets of HM Science

Contemporary HM’s ascent in public healthcare is extraordinary for its breadth and intensity, especially in the area of ready-to-use formulation creation. For scientists, current trends speak to longstanding interests that require some methodological innovations including reliance on the “-omic” sciences. Before considering scientific evidence base as the dynamic undertow of HM policy measures, many research gaps need to be addressed.


Stripped of its religiosity and of its mysticism, HM approach to disease treatment and disease prevention relies solely on the phytochemical constituents of plants as the chemotherapeutic and chemopreventive agents.

But, attempts to explain why a single herbal extracts can cure diseases of varied etiologies have been sporadic, heterogeneous and often of questionable grounding in clinical realism.  As promotion of health literacy of HM rapidly progresses, there is the increasing need to explain HM therapeutics in clearly understandable scientific terms. A current scientific hypothesis that explains most of the mechanistic conundrums posits that diverse herbal phytochemicals modify disease pathology through simultaneous regulation of multiple aberrant disease-causing pathways by interacting with different and multiple molecular targets simultaneously. The major and minor active constituents of plant extracts may individually exhibit multi-mechanism at multi-targets sites in the body either synergistically or antagonistically to relieve ailments. Alternatively, a single active constituent may act at a single target in an individual mechanism to effect remedy. All these mechanistic scenarios may surprisingly be operative in a single formulation and may complicate the downstream search for the reponsible bioactive principle(s).

Some insights as to the enormity of the task facing HM scientists can be gleaned from sketchy itemized discussions below.


Safety and Efficacy

Use of safe and efficacious HM medications are essential to ensuring the best possible clinical and health outcomes. There is a clear consensus around the idea that HM efficacy is historically derived and its inextricable link with safety is anecdotally assured but remains an open and debated scientific question. Scientifically, the chemical constituents of HM that endows the formulation with its efficacy may also be the source of adverse health and the basis for safety concerns.

Despite widespread nationwide use of phyto-therapies, the safety and efficacy of HM are not formally evaluated in pre-clinical trials. Unfortunately, efficacy and safety are established anecdotally after historical usage. In fact, safety and efficacy of formulations are judged post-use, indirectly, as those that provide fastest symptoms alleviation or attenuation without noticeable immediate adverse side effects. Studies of specific enzymatic molecular markers in animal models followed by clinical trial has the potential to lead to more efficacious, less toxic and better tolerated therapy for patients but it is unknown whether HM industries have the financial resources to conduct such trials that will provide valuable user feedback to assist the reformulation of optimized forms of HM formulations.

Efficacy may be a key factor in use decision and safety issue may worsen symptoms and lead to additional problematic health outcomes. But the efficacy and safety gap is not just an issue for science: it also has policy implications also. Which is why it seems worth asking: Are there policy interventions that could, realistically, help to improve efficacy and safety? Without recommendations from trusted peers and reports from regulatory authorities that indicate good treatment efficacy, excellent safety and good clinically relevant qualities of HM preparations, users may literally have to “try-out” all the available HM formulations on their symptom to identify the most efficacious and have to “screen-out” such formulations for favorable toxicity. Chronic and acute toxicity tests are now routinely performed and may be enforced by the FDB before permission is provided for marketing of formulations.

The regulatory safety and efficacy assessment of HM products are not rigorously evaluated in controlled settings that utilize live animal models. Consequently, providers and regulatory authorities cannot ensure through scientific means that safety and efficacy for HM products are comparable to AM prior to marketing. In the absence of such scientific information, HM users may improve safety by reducing doses and avoiding use in combination with adversely interacting AM drugs or with other antagonistic herbal constituents and declining use in combination with adverse substances including alcohol.


Standardization and Authentication

The wide availability and extensive variety of HM formulations in the increasing HM sales outlets raises public health concern about ineffective, fake and adulterated formulations. Standardization of formulation and authentication of medicinal plants constitute parts of good manufacturing practices that also assure repeated bioactivity of herbal extracts. A multi-disciplinary strategy can address issues of standardization of bioactive constituents through the use of distinctive chromatographic fingerprints and can focus on authentication of medicinal plants through the use of plant genetics.


Standardization of HM by active ingredients ensures that all manufactured batches of the same HM formulation contain the same number and dose of active ingredients or bioactive constituents. Although standardization is needed to assure repeated efficacy of batch-to-batch formulations and to assure HM quality improvement culture, its routine use is fraught with multiple inherent challenges. First, standardization requires the initial identification and quantitation of single bioactive constituents in a multi-constituent formulation using methods that rely on the use of specialized biochemical and analytical instruments and utilizing assays that are well beyond the financial means and the technical expertise of most HM providers. Second, the methodological endpoint is inexact. Distinct bioactive constituents within a single formulation may exert multiple biochemical effects at different molecular targets in diverse biological mechanisms that may occur through myriad mechanistic pathways to complicate a reductionist approach to the identification of a single bioactive component needed for efficient standardization.

Consequently, the current use of chromatographic fingerprints to profile broadly, as distinct peaks, the number and the dose of all chemical constituents (bioactive and inactive) present in a formulation is a progressive idea. Such formulation-specific distinct chromatographic fingerprints can be used to differentiate between formulations from different source manufacturers. Consequently, the chromatographic signatures of proven efficacious and safe formulation can be a useful standardization or reference standard for the examination of batch-to-batch marketed products for contents consistency and phytochemical reproducibility and for the identification of fake and adulterated formulations. However, use of chromatographic fingerprints in regulatory control may be nebulous since its requirement for formulation-specific multiple certified constituent reference standards cannot be easily met by HM providers.


A catalog of authenticated and scientifically labeled reference herbal plants for the most widely used formulations can be part of the FDB regulatory arsenals. Authentication of HM plants is necessary because of either deliberate replacement or accidental substitution of bioactive herbal plants with inactive subspecies.

Manufacturers routinely need to cross-check the botanical authenticity of their raw herbal plants with the FDB authenticated reference standard prior to formulation. Botanical identification by visual inspection is often complicated by plant subtypes that possess similar physical features as the authentic but have less or none of the species bioactive constituents. Batch-to-batch formulations of the same herbal plant sourced from different geographical locations will not lead to replicable results because plant secondary metabolism exhibit slight variability in mechanistic pathway activities depending on location. Genetic markers specific for each subtype can differentiate the authentic samples from other species subtypes and ultimately permit a less problematic enforcement of good formulation manufacturing practices. Simply put, authentication of plant samples have to move away from visual inspection into reliance on plant genetic biomarkers.

Standardization and authentication should precede clinical trials. Without standardization and authentication, use of different manufactured batches of any HM formulations for controlled clinical studies designed to evaluate safety and effectiveness will likely produce spurious results. Such inconclusive results are attributable to differences in phytochemical contents of different batches of formulations.

Bioactive Compound(s)

Bioactive compounds can, more broadly, be explored through the use of metabolomics. Since bioactive compounds are plant-specific and their biosynthesis are the culmination of unique plant secondary metabolism, qualitative metabolomic methods can be used to follow their biosynthesis and to explore in vitro laboratory methods of enhancing its yield in its specific metabolic pathway. Metabolomic characterizations of HM should be an integral component of the rigorous chemical evaluations of formulations. The mechanistic undercurrent for the biochemical transformation of the parent bioactive constituent to the potentially disease-preventive metabolites of interest can be teased out using metabolomics complemented by routine biochemical assays

More easily and routinely, interested HM providers can partner with KNUST to isolate, purify and structurally characterize bioactive constituent(s) in their branded formulations to pave the way for the chemical synthesis of the natural product constituent(s) or of its analogs for further bioactive studies. This bio-assay guided fractionation approach on a disease-related platform will lead eventually to the development of novel drug entities from a herbal medicinal extract source.

Molecular target identification

Molecular target identification open new realms of exploratory research into HM. Target identification is the most challenging undertaking requiring molecular biological, pharmacological and medicinal chemistry inputs. Undoubtedly improved experimental procedures are required for such future development of molecular targets that will ultimately illuminate the mechanism of action of the HM constituent(s).

The presence of multiple of bioactive constituents with inherently complex structural architecture within a single herbal preparations, does not readily allow for easy isolation, purification and characterization of a single pure bioactive species and for the identification of its target site as well as for the delineation of its mechanistic mode of therapeutic action. In most cases, the scientific assessments of HM are limited at the first stage by the lack of isolable pure bioactive compound. Consequently, follow-up mechanistic studies lack the rigorous specificity that characterizes the scientific assessment of AM drugs that have single bioactive constituent(s). But available new technologies and resource allocation can enable, at the least, the isolation and the structural identification of pure constituents to allow for inclusion of such characterized compounds in formulation content labels.


Herb-Herb and Herb-AM Drug Interaction

Synergistic and/or antagonistic interactions between bioactive constituent(s) from different plant extracts and between HM formulations and AM drugs are possible even at doses that are so low that they do not provide much relief or a physiological effect by itself. Adverse herb-drugs and herb-herb interaction can confound treatment and produce complications, elevate symptom burden and increase symptom distress, reduce health-related quality of life and even increase mortality when poorly-controlled. FDB needs to catalog all known and reported adverse HM reaction, HM-HM interactions and HM-drug interactions in a curated database for easy access to the public. Regulatory authorities can notify the general public and users on specific formulations that trigger potential adverse effects.

Since it is impossible to predict a priori phytochemicals that induce either synergistic or antagonistic effects at target sites when different formulations are co-used or when HM-AM drugs are co-used, users can be advised to avoid the co-administration of co-interacting HM formulations at the same time and to refrain from the simultaneous use of such co-interacting herbs with AM.

Concluding Thoughts

Although advocacy for and resources devoted to HM science have increased substantially worldwide, Ghana does not undertake rigorous [still suffers from lack of rigor in the sciences] clinical and scientific assessment of HM. Inadequate scientific infrastructure, excessively high analyses costs and problematic methodological endpoints have become critical barriers to the advancement of the study of the scientific underpinning of HM-based treatment. Chemical analyses with translational implications including isolation and characterization of bioactive constituent(s) of HM formulations and delineation of its biochemical mechanisms of action are time consuming, capital and state-of-the-art equipment intensive. Such biochemical studies are also fraught with numerous methodological challenges that are generally beyond the expertise of HM providers.

But pre-clinical studies critical for the efficacy and safety evaluation of herbal extracts are doable within Ghana’s technological constraints. Clinical studies are not enforced by regulatory authorities and are unprofitable for providers to undertake. As a consequence, providers are generally unwilling to undertake it. Consequently, pharmacological assessment including safety, efficacy, tolerability, pharmacokinetics, pharmacodynamics and therapeutic mode of action of bioactive constituent(s) are not scientifically assessed prior to marketing and use by Ghanaians. Other follow-up pharmacologic assessment including absorption, distribution, metabolism and excretion, and toxicity of bioactive constituents that are mostly dependent on isolated pure bioactive constituent are conveniently ignored??

Nevertheless a lot can be done within these constrainst. Small molecule modulators of cellular behavior can also be discovered to enhance mechanistic studies in biomedical research. This approach will also advance the science and knowledge base of HM to comparable levels worldwide. Ultimately scientific evidence will be generated to inform the use of medicinal herbs in a clinical environment that relies on the chemotherapeutic and chemopreventive properties of medicinal plants.

Strong partnerships among regulators, provider companies, academic researchers, patients, and physicians will inexorably provide a staging ground for HM science to take off. KNUST should as matter of priority motivate a wide coalition of partners toward the common goal of science-driven HM support.



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Herbal Medicine 1/4 01 October 2020
Herbal Medicine 2/4 01 October 2020
Herbal Medicine 4/4 01 October 2020
Fellowship 08 October 2020
The Final Goodbye 1/3 27 December 2020
The Final Goodbye 2/3 27 December 2020
The Final Goodbye 3/3 27 December 2020

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