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particles. A striking capability that has been reported for many nanoparticles is their abil-
ity to physically interact with the cell surfaces of some bacteria. In principle, the nature of
these interactions could be exploited to target metal nanomaterials to specific bacterial
cells [(
Lemire et al., 2013) and ref. therein]. Nanoparticle toxicity could be due to several
attributes, including traits that are particle specific (such as size, shape, or surface charge)
and traits that control the release of metal ions. The toxic mode of action of nanoparticles
has also been associated with ROS generation and membrane disruption. A growing num-
ber of reports indicate that the release of ions is a driving force behind the antimicrobial
properties of nanoparticles.
The formation of metal nanoparticles has been demonstrated in remedies from tradi-
tional Indian pharmacopeias. These pharmacopeias make extensive use of metals in reme-
dies whose preparation is complex and involves various successive heating/calcination
steps, in which various plants are gradually added. A few pioneering studies have shown
that these steps lead to the formation of metal nanoparticles (i.e.,
Kannan, Balaji, &
Kumar, 2017; Ruddaraju, Pammi, Guntuku, Padavala, & Kolapalli, 2020; Sharma, Sharma,
Kumar, & Yadav, 2015; Singh et al., 2019; Wijenayake, Abayasekara, Pitawala, & Bandara,
2016
). These nanoparticles will have very different properties from plants/metals alone,
and may therefore lead to different prescriptions, different modes of administration prop-
erties that remain to be studied.
Although various approaches have been developed to synthesize nanoparticles, recent
approaches have enabled us to synthesize them in a simple and environmentally friendly
way (
Ruddaraju et al., 2020). Many plants produce antioxidants, which are essential for
the formation of nanoparticles, and it turns out that certain metals spontaneously form
nanoparticles in a plant extract. Various authors have therefore used this ability to synthe-
size nanoparticles from therapeutic plant extracts, in order to obtain effective nanoparti-
cles, the characteristics of which would be reproducible, allowing more rigorous clinical
analysis (i.e.,
Chinnasamy, Chandrasekharan, & Bhatnagar, 2019; Khoobchandani et al.,
2020; Tiloke, Anand, Gengan, & Chuturgoon, 2018
). This would also make it possible to
combine traditional medicines and modern medical (nano)technologies. Various gold, sil-
ver, or copper nanoparticles have been obtained on this basis, some with antibacterial
properties (
Devanesan, Ponmurugan, Alsalhi, & Al-Dhabi, 2020; Tripathi, Modi, Narayan,
& Rai, 2019
). It is not impossible that traditional remedies, combining plants and metals,
could lead to the formation of such nanoparticles, without necessarily requiring thermal
transformation steps (heating, calcination, etc.)
Characterization of plantmetal combinations
Although the prospects may be interesting, the study of such combinations from tradi-
tional remedies is still in its infancy. Many obstacles still stand in the way. The processing
of these remedies is based on well-defined preparation protocols, which must be followed
faithfully. However, finding and analyzing these protocols from the historical literature do
not always allow for a faithful reconstruction. The resources are not always exactly
defined, their names may have changed, finding their current equivalent is not guaran-
teed. In addition, the protocols are only partial. The heating temperature, for examp le, is
474 14. The case of cutaneous infections’ remedies
Medicinal Plants as Anti-infectives
often not well explained, certain ’shortcuts’ used in the past are not easy to decipher, the
translation of the texts sometimes leaves some uncertainties.
Structurally and functionally characterizing these organometallic formulations will also
require to work on the whole remedy and not on each individual ingredient. The forma-
tion of organometallic molecules can only be obtained after scrupulously following the
manufacturing protocol. It is therefore also necessary to review the protocols for the identi-
fication and isolation of fractions/active molecules, which were often based on extractions
from the various dried plants alone, which were then fractionated by organic solvents.
The characterization of these molecules/organometallic particles will require the adapta-
tion of purification and characterization methods, which are often more technology-
intensive. It would also not be surprising if the minerals could be found in different forms
in the remedy (elemental, particulate) and that all these forms contribute to the properties
of the remedy. Some properties will also be difficult to reproduce in vitro (e.g., the irritant
effect) and will necessarily require an animal model.
Finally, reusing these remedies will require a great effort in terms of reproducibility/
standardization. Indeed, very fine variations in the protocol can have important conse-
quences on the formation of the different active molecules. Moreover, as these minerals
could be found in different forms, the toxicity of the remedy could reflect the balance
between the different forms, which would be more difficult to control.
Conclusion
There is no original origin for pharmacy. It was born with man, who has always sought
to relieve his physical suffering by using the remedies available to him in nature. Ancient
and medieval pharmacopeias contain thus vast information on the use of medical material,
whether vegetable, mineral, or animal. It is not unrealistic to think that these 1000-year-old
pharmacopeias still hold secrets that could have a significant impact on the composition of
today’s medicines (
Harrison & Connely, 2019). Their study could thus provide more than
only understanding the medieval mind.
References
Abd-El-Aziz, A. S., Agatemor, C., & Etkin, N. (2017). Antimicrobial resistance challenged with metal-based antimicro-
bial macromolecules. Biomaterials, 118,2750. Available from
https://doi.org/10.1016/j.biomaterials.2016.12.002.
Albada, B., & Metzler-Nolte, N. (2017). Highly potent antibacterial organometallic peptide conjugates. Accounts of
Chemical Research, 50, 25102518. Available from https://doi.org/10.1021/acs.accounts.7b00282.
Alu’datt, M. H., Rababah, T., Alhamad, M. N., Al-Mahasneh, M. A., Almajwal, A., Gammoh, S., ... Alli, I. (2017).
A review of phenolic compounds in oil-bearing plants: Distribution, identification and occurrence of phenolic
compounds. Food Chemistry, 218,99106. Available from
https://doi.org/10.1016/j.foodchem.2016.09.057.
Anawati, G. C., Me
´
dicaments, L., & L’Oeil, D. (1905). Chez Hunayn Ibn Isha
˜
q. Arabica, 21.
Bagchi, A., Mukherjee, P., Bhowmick, S., & Raha, A. (2015). Synthesis, characterization and antibacterial activity of a novel
curcumin metal complex. International Journal of Drug Development and Research, 7,1114. Available from
http://ijddr.
in/drug-development/synthesis-characterization-and-antibacterial-activity-of-a-novel-curcuminmetal-complex.pdf
.
Banin, E., Lozinski, A., Brady, K. M., Berenshtein, E., Butterfield, P. W., Moshe, M., ... Banin, E. (2008). The potential
of desferrioxamine-gallium as an anti-Pseudomonas therapeutic agent. Proceedings of the National Academy of
Sciences of the United States of America, 105, 1676116766. Available from
https://doi.org/10.1073/pnas.0808608105.
475References
Medicinal Plants as Anti-infectives
Barillo, D. J., & Marx, D. E. (2014). Silver in medicine: A brief history BC 335 to present. Burns: Journal of the
International Society for Burn Injuries, 40,S3S8. Available from
https://doi.org/10.1016/j.burns.2014.09.009.
Benoit, D. S. W., Sims, K. R., & Fraser, D. (2019). Nanoparticles for oral biofilm treatments. ACS Nano, 13,
48694875. Available from https://doi.org/10.1021/acsnano.9b02816.
Bonah, C., & du Stalinon, L. ’affaire (2007). Et ses conse
´
quences re
´
glementaires, 19541959, LA. Revue du
Praticien, 57, 15011505.
Bouamrane, F. (2010). Le traite
´
me
´
dical (Kita
ˆ
b al-Taysir) de Ibn Zuhr de Se
´
ville, vrin.
Chen, Y., Zou, J., Sun, H., Qin, J., & Yang, J. (2021). Metals in traditional Chinese medicinal materials (TCMM): A
systematic review. Ecotoxicology and Environmental Safety, 207, 111311. Available from
https://doi.org/
10.1016/j.ecoenv.2020.111311.
Chinnasamy, G., Chandrasekharan, S., & Bhatnagar, S. (2019). Biosynthesis of silver nanoparticles from Melia aze-
darach: Enhancement of antibacterial, wound healing, antidiabetic and antioxidant activities. International
Journal of Nanomedicine, 14, 98239836. Available from
https://doi.org/10.2147/IJN.S231340.
Chitambar, C. R. (2016). Gallium and its competing roles with iron in biological systems. Biochimica et Biophysica
Acta - Molecular Cell Research, 1863, 20442053. Available from https://doi.org/10.1016/j.bbamcr.2016.04.027.
Devanesan, S., Ponmurugan, K., Alsalhi, M. S., & Al-Dhabi, N. A. (2020). Cytotoxic and antimicrobial efficacy of
silver nanoparticles synthesized using a traditional phytoproduct, asafoetida gum. International Journal of
Nanomedicine, 15, 43514362. Available from
https://doi.org/10.2147/IJN.S258319.
Dolwett, H. H. A., & Sorensen, J. R. J. (1985). Historic uses of copper compounds in medicine. Trace Elements in
Medicine, 2,8087.
Egorova, K. S., & Ananikov, V. P. (2017). Toxicity of metal compounds: Knowledge and myths. Organometallics,
36, 40714090. Available from
https://doi.org/10.1021/acs.organomet.7b00605.
El-Sheikh, A. A., Ameen, S. H., & AbdEl-Fatah, S. S. (2018). Ameliorating iron overload in intestinal tissue of adult
male rats: Quercetin vs deferoxamine. Journal of Toxicology, 2018, 8023840. Available from
https://doi.org/
10.1155/2018/8023840
.
Ernst, E. (2002). Heavy metals in traditional Indian remedies. European Journal of Clinical Pharmacology, 57,
891896. Available from https://doi.org/10.1007/s00228-001-0400-y.
Golonka, R., Yeoh, B. S., & Vijay-Kumar, M. (2019). The iron tug-of-war between bacterial siderophores and innate
immunity. Journal of Innate Immunity, 11, 249262. Available from
https://doi.org/10.1159/000494627.
Greenberg, E. P., Banin, E., Banin, E., Berenshtein, E., & Chevion, M. (2007). Metallo-desferrioxamine complexes and
their use in the treatment of bacterial infections. Hadasit Medical Research Services and Development Co.
Gunawan, C., Teoh, W. Y., Marquis, C. P., & Amal, R. (2011). Cytotoxic origin of copper(II) oxide nanoparticles:
Comparative studies with micron-sized particles, leachate, and metal salts. ACS Nano., 5, 72147225.
Available from
https://doi.org/10.1021/nn2020248.
Harrison, F., & Connely, E. (2019). Could medieval medicine help the fight against antimicrobial resistance?
Making the medieval relevant. De Gruyter.
Hatamie, S., Nouri, M., Karandikar, S. K., Kulkarni, A., Dhole, S. D., Phase, D. M., & Kale, S. N. (2012).
Complexes of cobalt nanoparticles and polyfunctional curcumin as antimicrobial agents. Materials Science and
Engineering C, 32,9297. Available from
https://doi.org/10.1016/j.msec.2011.10.002.
Hatcher, H., Planalp, R., Cho, J., Torti, F. M., & Torti, S. V. (2008). Curcumin: From ancient medicine to current
clinical trials. Cellular and Molecular Life Sciences, 65, 16311652. Available from https://doi.org/10.1007/
s00018-008-7452-4
.
Hemeg, H. A. (2017). Nanomaterials for alternative antibacterial therapy. International Journal of Nanomedicine, 12,
82118225. Available from https://doi.org/10.2147/IJN.S132163.
Hu, Y., Zhu, Y., & Lu, N. H. (2017). Novel and effective therapeutic regimens for Helicobacter pylori in an era of
increasing antibiotic resistance. Frontiers in Cellular and Infection Microbiology, 7, 168. Available from
https://
doi.org/10.3389/fcimb.2017.00168.
Kannan, N., Balaji, S., & Kumar, N. V. A. (2017). Structural and elemental characterization of traditional Indian
Siddha formulation: Thalagak karuppu. Journal of Ayurveda and Integrative Medicine, 8, 184189. Available from
https://doi.org/10.1016/j.jaim.2016.11.005.
Khoobchandani, M., Katti, K. K., Karikachery, A. R., Thipe, V. C., Srisrimal, D., Mohandoss, D. K. D., ... Katti,
K. V. (2020). New approaches in breast cancer therapy through green nanotechnology and nano-ayurvedic
476 14. The case of cutaneous infections’ remedies
Medicinal Plants as Anti-infectives
medicine pre-clinical and pilot human clinical investigations. International Journal of Nanomedicine, 15,
181197. Available from
https://doi.org/10.2147/IJN.S219042.
Lanoe
¨
, C. (2002). La ce
´
ruse dans la fabrication des cosme
´
tiques sous l’Ancien Re
´
gime (XVIe-XVIIIe sie
`
cles). In: Techniques
& Culture. Revue Semestrielle d’anthropologie Des Techniques. Available from https://doi.org/10.4000/tc.224.
Le Bonniec, H., & Histoire naturelle, P l’A. (1953). Livre XXXIV (Des Me
´
taux et de la sculpture), Les Belles Lettres.
Lemire, J. A., Harrison, J. J., & Turner, R. J. (2013). Antimicrobial activity of metals: Mechanisms, molecular targets
and applications. Nature Reviews Microbiology, 11, 371384. Available from
https://doi.org/10.1038/nrmicro3028.
Lev, E. (2002). Medicinal exploitation of inorganic substances in the Levant in the Medieval and early Ottoman
periods. Adler Museum Bulletin, 28,1116.
Miethke, M., & Marahiel, M. A. (2007). Siderophore-based iron acquisition and pathogen control. Microbiology and
Molecular Biology Reviews, 71, 413451. Available from https://doi.org/10.1128/MMBR.00012-07.
Mikulski, M. A., Wichman, M. D., Simmons, D. L., Pham, A. N., Clottey, V., & Fuortes, L. J. (2017). Toxic metals in ayur-
vedic preparations from a public health lead poisoning cluster investigation. International Journal of Occupational and
Environmental Health, 23, 187192. Available from
https://doi.org/10.1080/10773525.2018.1447880.
Mislin, G. L. A., & Schalk, I. J. (2014). Siderophore-dependent iron uptake systems as gates for antibiotic Trojan
horse strategies against Pseudomonas aeruginosa. Metallomics, 6, 408420. Available from https://doi.org/
10.1039/c3mt00359k
.
Nairz, M., Dichtl, S., Schroll, A., Haschka, D., Tymoszuk, P., Theurl, I., & Weiss, G. (2018). Iron and innate antimi-
crobial immunity—Depriving the pathogen, defending the host. Journal of Trace Elements in Medicine and
Biology, 48, 118133. Available from
https://doi.org/10.1016/j.jtemb.2018.03.007.
Ong, Y. C., & Gasser, G. (2019). Organometallic compounds in drug discovery: Past, present and future. Drug
Discovery Today: Technologies. Available from https://doi.org/10.1016/j.ddtec.2019.06.001.
Parascandola, J. (2009). From mercury to miracle drugs: Syphilis therapy over the centuries. Pharmacy in History,
51,1423.
Patra, M., Gasser, G., & Metzler-Nolte, N. (2012). Small organometallic compounds as antibacterial agents. Dalton
Transactions, 41, 63506358. Available from
https://doi.org/10.1039/c2dt12460b.
Perraud, Q., Kuhn, L., Fritsch, S., Graulier, G., Gasser, V., Normant, V., ... Schalk, I. J. (2020). Opportunistic use
of catecholamine neurotransmitters as siderophores to access iron by Pseudomonas aeruginosa. Environmental
Microbiology. Available from
https://doi.org/10.1111/1462-2920.15372.
Refat, M. S. (2013). Synthesis and characterization of ligational behavior of curcumin drug towards some transition
metal ions: Chelation effect on their thermal stability and biological activity. Spectrochimica Acta - Part A: Molecular
and Biomolecular Spectroscopy, 105, 326337. Available from
https://doi.org/10.1016/j.saa.2012.12.041.
Riva, M. A., Lafranconi, A., D’Orso, M. I., & Cesana, G. (2012). Lead poisoning: Historical aspects of a paradig-
matic \occupational and environmental disease\. Safety and Health at Work, 3,1116. Available from https://
doi.org/10.5491/SHAW.2012.3.1.11.
Ruddaraju, L. K., Pammi, S. V. N., Guntuku, G. S., Padavala, V. S., & Kolapalli, V. R. M. (2020). A review on anti-
bacterials to combat resistance: From ancient era of plants and metals to present and future perspectives of
green nano technological combinations. Asian Journal of Pharmaceutical Sciences, 15,4259. Available from
https://doi.org/10.1016/j.ajps.2019.03.002.
Ruparelia, J. P., Chatterjee, A. K., Duttagupta, S. P., & Mukherji, S. (2008). Strain specificity in antimicrobial activ-
ity of silver and copper nanoparticles. Acta Biomaterialia, 4, 707716. Available from https://doi.org/10.1016/
j.actbio.2007.11.006
.
Saad, B., & Said, O. (2011). Greco-Arab and Islamic herbal medicine: Traditional system, ethics, safety, efficacy, and regula-
tory Issues. Wiley.
Sakihama, Y., Cohen, M. F., Grace, S. C., & Yamasaki, H. (2002). Plant phenolic antioxidant and prooxidant activi-
ties: Phenolics-induced oxidative damage mediated by metals in plants. Toxicology, 177,6780. Available from
https://doi.org/10.1016/S0300-483X(02)00196-8.
Saper, R. B., Phillips, R. S., Sehgal, A., Khouri, N., Davis, R. B., Paquin, J., ... Kales, S. N. (2008). Lead, mercury,
and arsenic in US- and Indian-manufactured Ayurvedic medicines sold via the internet. Journal of the American
Medical Association, 300, 915923. Available from
https://doi.org/10.1001/jama.300.8.915.
Schalk, I. J., & Cunrath, O. (2016). An overview of the biological metal uptake pathways in Pseudomonas aeruginosa.
Environmental Microbiology, 18, 32273246. Available from https://doi.org/10.1111/1462-2920.13525.
477References
Medicinal Plants as Anti-infectives
Schatzschneider, U. (2018). Antimicrobial activity of organometal compounds: Past, present, and future prospects.
Advances in bioorganometallic chemistry (pp. 173192). Germany: Elsevier. Available from
https://doi.org/
10.1016/B978-0-12-814197-7.00009-1
.
Sharma, K. C., Sharma, U., Kumar, V., & Yadav, Y. (2015). Some observations of the zinc-metals based prepara-
tions and its properties in ayurveda with regard to stability of medicines in the nano state. International Journal
of Research in Ayurveda & Pharmacy, 6(1), 3034. Available from
https://doi.org/10.7897/2277-4343.0618.
Shaw, D., Leon, C., Kolev, S., & Murray, V. (1997). Traditional remedies and food supplements. A 5-year toxicological
study (1991-1995). Drug Safety, 17,342356. Available from https://doi.org/10.2165/00002018-199717050-00006.
Sierra, M. A., Casarrubios, L., & de la Torre, M. C. (2019). Bio-organometallic derivatives of antibacterial drugs.
Chemistry - A European Journal, 25, 72327242. Available from
https://doi.org/10.1002/chem.201805985.
Singh, R. K., Kumar, S., Aman, A. K., Karim, S. M., Kumar, S., & Kar, M. (2019). Study on physical properties of
ayurvedic nanocrystalline Tamra Bhasma by employing modern scientific tools. Journal of Ayurveda and
Integrative Medicine, 10,8893. Available from
https://doi.org/10.1016/j.jaim.2017.06.012.
Snafi, A. E. A. (2018). Arabian medicinal plants with dermatological effects - Plant based review (part 1). IOSR
Journal of Pharmacy (IOSRPHR), 8,4473.
Song, Y. M., Xu, J. P., Ding, L., Hou, Q., Liu, J. W., & Zhu, Z. L. (2009). Syntheses, characterization and biological
activities of rare earth metal complexes with curcumin and 1,10-phenanthroline-5,6-dione. Journal of Inorganic
Biochemistry, 103, 396400. Available from https://doi.org/10.1016/j.jinorgbio.2008.12.001.
Sotiriou, G. A., & Pratsinis, S. E. (2010). Antibacterial activity of nanosilver ions and particles. Environmental
Science and Technology, 44, 56495654. Available from
https://doi.org/10.1021/es101072s.
Squibb, K. S., & Fowler, B. A. (1981). Relationship between metal toxicity to subcellular systems and the carcino-
genic response. Environmental Health Perspectives, 40, 181188.
Tapsoba, I., Arbault, S., Walter, P., & Amatore, C. (2010). Finding out Egyptian Gods’ secret using analytical
chemistry: Biomedical properties of Egyptian black makeup revealed by amperometry at single cells.
Analytical Chemistry, 82, 457460. Available from
https://doi.org/10.1021/ac902348g.
Tiloke, C., Anand, K., Gengan, R. M., & Chuturgoon, A. A. (2018). Moringa oleifera and their phytonanoparticles:
Potential antiproliferative agents against cancer. Biomedicine and Pharmacotherapy, 108, 457466. Available from
https://doi.org/10.1016/j.biopha.2018.09.060.
Tripathi, D., Modi, A., Narayan, G., & Rai, S. P. (2019). Green and cost effective synthesis of silver nanoparticles
from endangered medicinal plant Withania coagulans and their potential biomedical properties. Materials
Science and Engineering C, 100, 152164. Available from
https://doi.org/10.1016/j.msec.2019.02.113.
Vaidya, V. S., & Mehendale, H. M. (2014). Mercuric chloride (HgCl
2
). Encyclopedia of toxicology (Third Edition,
pp. 203206). United States: Elsevier. Available from
https://doi.org/10.1016/B978-0-12-386454-3.00330-4.
Vimbela, G. V., Ngo, S. M., Fraze, C., Yang, L., & Stout, D. A. (2017). Antibacterial properties and toxicity from
metallic nanomaterials. International Journal of Nanomedicine, 12, 39413965. Available from
https://doi.org/
10.2147/IJN.S134526
.
Wanninger, S., Lorenz, V., Subhan, A., & Edelmann, F. T. (2015). Metal complexes of curcumin Synthetic strate-
gies, structures and medicinal applications. Chemical Society Reviews, 49865002. Available from https://doi.
org/10.1039/C5CS00088B.
Wijenayake, A. U., Abayasekara, C. L., Pitawala, H. M. T. G. A., & Bandara, B. M. R. (2016). Antimicrobial poten-
tial of two traditional herbometallic drugs against certain pathogenic microbial species. BMC Complementary
and Alternative Medicine, 16, 365. Available from
https://doi.org/10.1186/s12906-016-1336-1.
Wilson, B. R., Bogdan, A. R., Miyazawa, M., Hashimoto, K., & Tsuji, Y. (2016). Siderophores in iron metabolism:
From mechanism to therapy potential. Trends in Molecular Medicine, 22, 10771090. Available from https://
doi.org/10.1016/j.molmed.2016.10.005
.
Wu, Q., Lu, Y. F., Shi, J. Z., Liang, S. X., Shi, J. S., & Liu, J. (2011). Chemical form of metals in traditional medicines
underlines potential toxicity in cell cultures. Journal of Ethnopharmacology, 134, 839843. Available from
https://doi.org/10.1016/j.jep.2011.01.031.
Xianglin, S., Castranova, V., Vallyathan, V., & Perry, W. G. (2001). Molecular mechanisms of metal toxicity and carci-
nogenesis. Springer.
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i
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,A
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., al-D
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s, Q., Chadli, A., & Hemrit, A. (2005). Abre
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478 14. The case of cutaneous infections’ remedies
Medicinal Plants as Anti-infectives
CHAPTER
15
Improved traditional medicine for
infectious disorders in Mali
Rokia Sanogo
1,2
, Mahamane Haı
¨
dara
2
and Adama De
´
nou
2
1
Department of Traditional Medicine, Bamako, Mali
2
Faculty of Pharmacy, University of
Sciences, Techniques and Technologies of Bamako, Mali
Introduction
African traditional medicine (TM) is a cultural heritage and a reservoir of knowledge
still largely untapped. It offers possibilities of effective, available, accessible, acceptable,
and affordable treatments for the common diseases in African rural communities. The
World Health Organization (WHO) estimates that the vast majority of rural populations in
developing countries use the resources of TM for their health needs (
WHO, 2001). The use
of plant-based systems continues to play an essent ial role in health care. It has been esti-
mated that approximately 80% of the population in developing co untries depend on TM
for their primary health care (
World Health Organization, 2002). In Ghana, Mali, Nigeria,
and Zambia, the first line of treatment for 60% of the children with high fevers, resulting
from malaria, is the use of herbal medicines at home (
WHO, 2004). Since the declaration of
Alma Ata in 1978, the WHO has recommended the inclusion of TM and the pharmacopeia
in primary health care (
WHO, 1978).
In 2000 WHO Africa reaffirmed the usefulness and desirability of the inclusion in the
armamentarium of traditional remedies, which gave evidence of safety, efficacy, and qual-
ity (
WHO, Fiftieth session of the WHO regional committee for Africa, 2002). In 2001 the
Abuja Declaration of Heads of State and Government of the African Union focused on the
research about the resources of TM for supporting Malaria, HIV AIDS, tuberculosis, and
other priority diseases treatments. The same year, the WHO Africa launched the African
Decade of TM (200110). In 2008 30 years after Alma Ata, the WHO reaffirmed the need
of the revival of primary health care (
WHO, Ouagadougou Declaration on Primary Health
Care, & Health Systems in Africa: Achieving Better Health for Africa in the New
Millennium, 2008
). The fifth session of the Conference of Ministers of Health in Windhoek,
Namibia, in April 2011, approved the report of the end of decade review (
African Union,
479
Medicinal Plants as Anti-infectives
DOI:
https://doi.org/10.1016/B978-0-323-90999-0.00004-5 Copyright © 2022 Elsevier Inc. All rights reserved.
Fifth Ordinary Session of the African Union Conference of Ministers of Health, 2011) and
recommended the renewal of the decade and the development of the plan of action for
implementation of the second Decade of African TM (201120). An interesting point of
the plan of action of this new decade is to continue the research and the development of
TM and medicinal plants to produce evidence on the safety, efficacy, and quality of new
phytodrugs.
In Mali, the sanitary situation is characterized by a predominance of many endemic and
epidemic diseases, with a lack of qualified health workers, medicines, and equipment. To
improve their state of health, people are using both conventional medicine and TM. The
TM, being a significant element in the cultural patrimony, still remains the main recourse
for a large majority of people for treating health problems. A high level of Malian
Government commitment supported the research and development on TM, with the crea-
tion of the first institute for the study on medicinal plants in 1968. Today, this institute is the
Department of Traditional Medicine (DMT as abbreviation of its French name) within the
National Institute for Research on Public Health (INRSP as abbreviation of its French name),
technical institution of the Ministry of Health and Ministry of Scientific Research of Mali,
burdened for the policy of TM resources valorization (PractitionersPracticsProducts).
This institute is a collaborating center of the WHO in the research on TM. The main objec-
tives of the DMT are to assure the collaboration between traditional and conventional
medicines and to produce medicines from local resources, in particular medicinal plants
(
Ms/INRSP/DTM, 2005).
The DMT has been a collaborating center of the WHO and is today a center of excel-
lence of the West African Health Organization (WAHO) of the ECOWAS region in terms
of the valorization of TM resources. The DMT has a strategic partnership with the holders
of traditional knowledge and know-how in the field of health, mainly through the Malian
Federation of Associations of Therapists and Herbalists.
The main activity of the DMT is the resea rch and development of medicinal products
from medicinal plants, called improved traditional medicines (ITMs). These ITMs make a
specific contribution to people’s access to quality health care for the management, among
other things, of infectious diseases.
This article will review ITMs that are indicated for the management of infectious diseases.
General information on improved traditional medicines
Definition
ITMs are medicines derived from the local traditional pharmacopeia, with determined
toxicity limits, pharmacological activity confirmed by scientific research, quantified dos-
age, and quality controlled when they are marketed (
Ms/INRSP/DTM, 2005).
Regulatory framework
Decree No. 04557/P-RM of December 01, 2004 establishing market ing authorizations
(MA) for medicinal products for human and veterinary use.
480 15. Improved traditional medicine for infectious disorders in Mali
Medicinal Plants as Anti-infectives
Interministerial Order No. 052203/Ms-MEP-SG of September 20, 2005 determining the
terms and conditions for applying for MA for medicinal products for human and veteri-
nary use.
Interministerial Order No. 052440/Ms-MEF-MEP-SG of October 12, 2005 setting the
rate and terms of the fixed duty relating to MAs for medicinal products for human and
veterinary use. The MA application files for pharmaceutical specialties for human or veter-
inary use concern (1) Generic essential drugs in International Nonproprietary Name from
the National list of essential drugs and (2) Medicinal plant-based drugs (drugs from the
traditional pharmacopeia).
Categories of improved traditional medicines
The categories are defined in Article 10:
Article 10: The term “drug derived from the traditional category 1 pharmacopeia” is
understood to mean any drug prepared by the traditional health practitioner for a patient,
extemporaneously with fresh or dry raw materials generally of short duration.
The term “drug derived from the traditional category 2 pharmacopeia” means any drug
derived from the traditional pharmacopeia commonly used in the community, prepared in
advance and whose active components of which it is composed are crude raw materials.
The term “medicinal product derived from the traditional category 3 pharmacopeia”
means any medicinal product resulting from scientific research and whose active compo-
nents are standardized extracts, prepared in advance.
By “drug derived from the traditional pharmacopeia of category 4” is meant any drug
resulting from scientific research and whose active components are purified molecules.
Marketing authoriz ation files for ITMs in Mali
In Mali, the MA application files for pharmaceutical specialties for human or veterinary
use, in particular, (1) Generic essential drugs in International Nonproprietary Name from
the National list of essential drugs: (2) Medicines based on medicinal plants (medicines
derived from the traditional pharmacopeia) classified according to the categories men-
tioned above.
Category 1 drugs are not subject to approval and MA.
Categories 2, 3, and 4 must be the object of obtaining the MA and in Mali the MA
request is addressed to the Directorate of Pharmacy and Medicines. The composition of
the file depends on the category. MA is granted by decision of the competent authority
after technical advice from the National Marketing Authorization Commission, made up
of experts from different fields (
Arre
ˆ
te
´
Ministe
´
riel No. 052203/Ms-MEP-SG du 20
Septembre 2005, 2005
):
According to Article 11, the MA application file for traditional herbal medicines written
in French must include:
For traditional drugs of category 2, the file is said to be of the light type, and comprises
three subfiles which are:
481Marketing authorization files for ITMs in Mali
Medicinal Plants as Anti-infectives
Administrative subfile: it includes:
• A letter of motivation addressed to the Ministry of Health
• A presentation of the production institution
• A copy of the deed authorizing the creation of the production institution
• Samples (10) of the sale model of the product
• Proof of payment of registration fees
• A wholesale price proposal excluding tax (PGHT from the French spelling).
Pharmaceutical subfile:
• Complete monographs of plants used as raw material
• The methods and stages of preparation and production
• A report on good manufacturing practices (GMP)
• An analytical expert report specifying
• The method of quality control of raw materials
• The results of stability and quality control tests of raw materials and excipients
• The method and results of control of products during manufacture
• The results of the quality control of the finished product
• The results of the stability tests of the finished product.
Toxico-clinical subfile:
• An expert report showing a long experience of using the drug in its current form or in
its traditional form (at least 20 years)
• Known toxicological risks must be presented in detail (risks of dose-dependent and/or
independent toxicity)
• The risks associated with the misuse of the drug as well as the possibilities of physical
or psychological dependence must also be indicated.
For traditional drugs of category 3 and 4, the file includes the following subfiles:
Administrative subfile: it includes
• A letter of motivation addressed to the Ministry of Health
• A presentation of the production institution
• A copy of the deed authorizing the creation of the production institution
• Samples (10) of the sale model of the product
• Proof of payment of registration fees
• The memorandum of understanding between the manufacturer and the research
institute
• A wholesale price proposal excluding tax (PGHT from the French spelling).
Pharmaceutical subfile (category 3):
• Complete monographs of plants used as raw material
• The methods and stages of preparation and production
• A report on GMP
• An analytical expert report
• The method of quality control of raw materials
482 15. Improved traditional medicine for infectious disorders in Mali
Medicinal Plants as Anti-infectives
• The results of stability and quality control tests of raw materials and excipients
• The method and results of control of products during manufacture
• The results of the quality control of the finished product
• The results of the stability tests of the finished product.
Pharmacological and toxicological subfile:
• Pharmacodynamic data
• Review of the literature on pharmacology and toxicology
• The results of acute and subchronic toxicity tests
• An expert report on the tests carried out.
Clinical subfile:
• An authorization for clinical trials, issued by the competent national authority
(recognized body or ethics committee)
• A clinical trial protocol according to standard methods (Phase I and II)
• The results of clinical trials
• An expert report on the clinical trials carried out.
Constitution of safety, efficiency, and quality data:
• The safety, efficacy, and quality data obtained are used to constitute the MA files.
• For the development of ITMs, DMT is carrying out research activities using a
methodology that goes through a long process.
• The different stages consist of collecting information on traditional recipes for the
management of infectious diseases, identifying medicinal plants that are used to
prepare recipes, harvesting plant raw materials, phytochemical investigations,
preclinical studies (toxicological, pharmacodynamic), drug formulation tests,
ethnomedical evidence studies and clinical trials (
Sanogo, 2014).
• Collection of information: Ethnob otanical surveys are carried out by a multidisciplinary
team in order to collect information on traditional recipes and medicinal plants used in
the traditional treatment of infectious diseases. The approach consists in selecting
remedies and medicinal plants according to the indication of traditional healers in
certain contexts of use. The indication is generally related to the symptoms and signs of
the diseases. Other data, such as preparation of remedies, claims for use, including
dosage, are also collected.
• Identification of medicinal plants and bibliographical review: This involves conducting
research to review scientific literature to collect preclinical and clinical data on plants
primarily used for the management of the same disease.
• Preclinical and clinical studies: Additional stu dies are carr ied out on selected plants,
including characterization of chemical constituents of aqueous and organic extracts,
toxicity estimation. The results of the preclinical study allow, in addition to confirming
the safety and efficacy of the extracts, the determination of the doses, dosages, and form
of use. The proposed formulation is subject to observational studies and if necessary for
a clinical trial carried out on the basis of a protocol approved by a scientific and ethics
committee.
483Marketing authorization files for ITMs in Mali
Medicinal Plants as Anti-infectives