SPAGYRIC HERBALISM
Compound derived from Brazilian plant exhibits action against parasite that causes visceral leishmaniasis
The researchers synthesized a molecule inspired by a substance present in Nectandra leucantha (canela-seca or canela-branca). Animal trials have produced promising results.
Fundação de Amparo à Pesquisa do Estado de São Paulo
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Electron microscope image of Leishmania, structure of synthetic compound, and rat
view moreCredit: André Gustavo Tempone
A compound derived from Nectandra leucantha, a tree native to southern Brazil (local names canela-seca or canela-branca), has the potential to be used to treat visceral leishmaniasis, a neglected tropical disease associated with poverty, malnutrition, poor housing and lack of basic sanitation.
The disease is almost always fatal if left untreated. Most cases occur in Brazil, East Africa and India, according to the World Health Organization (WHO). An estimated 50,000-90,000 new cases and 20,000-50,000 deaths occur worldwide annually, with only 25%-45% of cases being reported to WHO.
The disease is caused by a protozoan parasite transmitted by sandfly bite, and characterized by long bouts of fever, loss of weight and muscle strength, enlargement of the spleen and liver, and anemia.
An article by researchers affiliated with institutions in Brazil, the United Kingdom and Portugal, published in the journal Antimicrobial Agents and Chemotherapy, reports the findings of a study showing that the substance killed Leishmania infantum, the parasite that causes the disease, selectively (i.e. without affecting host cells).
The first step in the study, which was supported by FAPESP, was synthesis of a compound similar to dehydrodieugenol B, a neolignan found naturally in N. leucantha and isolated originally by João Lago, full professor at the Federal University of the ABC (UFABC) in São Paulo state, Brazil. The synthesis was performed by Edward Anderson, a professor of organic chemistry at the University of Oxford in the UK.
“We used this substance as a prototype, a model based on which we could design novel versions of the molecule [with minor structural variations] and test them one by one on the parasite in vitro with the aim of optimizing its action,” said André Gustavo Tempone, principal investigator for the study and a researcher at Butantan Institute’s Physiopathology Laboratory in Brazil.
In this manner, the researchers obtained a molecule four times more powerful than the prototype. However, in vivo tests involving animals were disappointing because the optimized compound circulated in the rodents’ organism for less than ten minutes, and the study was unable to make progress. “The fact that the substance circulated for such a short time in the rats’ bodies suggested that the ensuing stages of the research would fail. It became clear that the substance wouldn’t produce the expected results,” Tempone said.
The team then focused on additional optimization of the molecule with the aim of enhancing its bioavailability so that it would remain for longer in the animal’s organism. After several chemical optimization processes conducted in vitro in partnership with Maiara Amaral, a student of Tempone’s who was on an internship at Oxford University and used the project as her PhD thesis, they arrived at a more potent molecule whose mean plasma half-life reached 21 hours.
Pharmacokinetic studies measuring the time required for the substance to be absorbed, distributed, metabolized and excreted showed that it circulated in the rat’s organism for a period 100 times longer than that observed initially.
Based on the in vitro analysis, the researchers concluded both that the novel substance was more potent in combating L. infantum, and that it did no damage to host cells. They also investigated its action mechanism, showing that it caused an irreversible collapse of the parasite’s energy mechanism (ATP) due to an increase in calcium, while reducing host cell inflammation, a key factor in the treatment of visceral leishmaniasis. With these good results behind them, the scientists plan to advance farther in animal trials. “We need to analyze the action of the compound in rodents with leishmaniasis in order to assess its efficacy and the doses required for treatment,” Tempone said.
Their long-term goal is to use the compound to produce medications against visceral leishmaniasis, but a great deal of work still has to be done to achieve this objective. As Tempone recalled, novel drugs take around 15 years to come to market, the development process involving rigorous tests and trials to ensure that the active ingredient is totally safe before clinical trials involving humans can be approved.
This research is extremely important, he added, as the large pharmaceutical companies are not interested in developing drugs for neglected diseases such as visceral leishmaniasis. “Brazil has one of the most outstanding biodiversities in the world, and a huge abundance of available chemical structures that can be copied and used in medications. If we don’t invest in combating this disease, the rich countries where it isn’t endemic certainly won’t,” he said.
About FAPESP
The São Paulo Research Foundation (FAPESP) is a public institution with the mission of supporting scientific research in all fields of knowledge by awarding scholarships, fellowships and grants to investigators linked with higher education and research institutions in the state of São Paulo, Brazil. FAPESP is aware that the very best research can only be done by working with the best researchers internationally. Therefore, it has established partnerships with funding agencies, higher education, private companies, and research organizations in other countries known for the quality of their research and has been encouraging scientists funded by its grants to further develop their international collaboration.
Journal
Antimicrobial Agents and Chemotherapy
Article Title
Synthesis of a dehydrodieugenol B derivative as a lead compound for visceral leishmaniasis—mechanism of action and in vivo pharmacokinetic studies
Exploring the eco-friendly future of antibiotic particles
How goji berries can be used to create silver nanoparticles
American Institute of Physics
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An illustration of the preparation of goji berries for silver nanoparticle synthesis.
view moreCredit: Kamran Alam et al.
WASHINGTON, Jan. 7, 2025 – As the search for sustainability permeates all fields, researchers are turning to a unique organic source for creating antibacterial silver nanoparticles (Ag-NPs) – the humble goji berry.
Goji berries are a ubiquitous superfood known for a multitude of health benefits, including their antibiotic properties. In research published in AIP Advances, by AIP Publishing, researcher Kamran Alam from Sapienza University of Rome along with others from NED University of Engineering and Technology and King Saud University found an effective way to harvest silver nanoparticles from these berries.
“Silver nanoparticles are responsible for disrupting the cell membrane structure, which can generate reactive oxygen species used for inhibiting bacterial growth,” explained Alam.
Silver nanoparticles can be generated using a number of chemical techniques, but green solutions that use biological sources like fruit or leaf extracts are preferred because they save on energy and are nontoxic, nonhazardous, and biologically compatible with humans.
In this interdisciplinary undertaking, Alam and researchers demonstrated a technique for the synthesis of silver nanoparticles using store-bought goji berries.
“Goji berries are easily and locally available in the botanic garden and are rich in bioactive compounds that have natural reducing and stabilizing agents, eliminating the need for additional capping agents during processing,” Alam said.
Alam and the team created silver nanoparticles by drying, grinding, and then filtering the goji berries to create an extract. Then, they added chemical silver nitrate (AgNO3) and reduced the solution.
Using visualization techniques such as X-ray diffraction, Ultraviolet-Visible (UV-Vis) Spectroscopy, and Fourier Transform Infrared (FT-IR) Spectroscopy, the team confirmed the presence of silver nanoparticles. The nanoparticles were also viewed under a microscope and tested for their antimicrobial activity against Staphylococcus aureus, a gram-positive bacterium that causes staph infections among other diseases.
In the future, Alam plans to study the cellular toxicity and biocompatibility of the nanoparticles synthesized from these berries, which could positively contribute to biomedical research.
“This is a simple and straightforward synthesis method which does not need additional chemicals or complex equipment and can be scaled up for industrial applications,” he said.
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The article “Ecofriendly synthesis of silver nanoparticles using metallic solution-based goji berry extract for their antibacterial properties” is authored by Abdul Rauf Jamali, Waseem Khan, Salahuddin Khan, Ahmed Ahmed Ibrahim, and Kamran Alam. It will appear in AIP Advances on Jan. 7, 2025 (DOI: 10.1063/5.0237276). After that date, it can be accessed at https://doi.org/10.1063/5.0237276.
ABOUT THE JOURNAL
AIP Advances is an open access journal publishing in all areas of physical sciences—applied, theoretical, and experimental. The inclusive scope of AIP Advances makes it an essential outlet for scientists across the physical sciences. See https://pubs.aip.org/aip/adv.
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Journal
AIP Advances
Article Title
Ecofriendly synthesis of silver nanoparticles using metallic solution-based goji berry extract for their antibacterial properties
Article Publication Date
7-Jan-2025
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