Papers by Pamela Weathers
Agronomia: Elo da Cadeia Produtiva 5
Todo o conteúdo deste livro está licenciado sob uma Licença de Atribuição Creative Commons. Atrib... more Todo o conteúdo deste livro está licenciado sob uma Licença de Atribuição Creative Commons. Atribuição 4.0 Internacional (CC BY 4.0). O conteúdo dos artigos e seus dados em sua forma, correção e confiabilidade são de responsabilidade exclusiva dos autores. Permitido o download da obra e o compartilhamento desde que sejam atribuídos créditos aos autores, mas sem a possibilidade de alterá-la de nenhuma forma ou utilizá-la para fins comerciais.
bioRxiv (Cold Spring Harbor Laboratory), Jan 8, 2021
Pathogens, Feb 1, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Journal of Ethnopharmacology, May 1, 2023
Journal of Ethnopharmacology, Nov 1, 2020
Emergence of drug-resistant and multidrug-resistant Mycobacterium tuberculosis (Mtb) strains is a... more Emergence of drug-resistant and multidrug-resistant Mycobacterium tuberculosis (Mtb) strains is a major barrier to tuberculosis (TB) eradication, as it leads to longer treatment regimens and in many cases treatment failure. Thus, there is an urgent need to explore new TB drugs and combinations, in order to shorten TB treatment and improve outcomes. Here, we evaluated the potential of two Asian and African traditional medicinal plants, Artemisia annua, a natural source of artemisinin (AN), and Artemisia afra, as sources of novel antitubercular agents. Aim of the study: Our goal was to measure the activity of A. annua and A. afra extracts against Mtb as potential natural and inexpensive therapies for TB treatment, or as sources of compounds that could be further developed into effective treatments. Materials and methods: The minimum inhibitory concentrations (MICs) of A. annua and A. afra dichloromethane extracts were determined, and concentrations above the MICs were used to evaluate their ability to kill Mtb and Mycobacterium abscessus in vitro. Results: Previous studies showed that A. annua and A. afra inhibit Mtb growth. Here, we show for the first time that Artemisia extracts have a strong bactericidal activity against Mtb. The killing effect of A. annua was much stronger than equivalent concentrations of pure AN, suggesting that A. annua extracts kill Mtb through a combination of AN and additional compounds. A. afra, which produces very little AN, displayed bactericidal activity against Mtb that was substantial but weaker than that of A. annua. In addition, we measured the activity of Artemisia extracts against Mycobacterium abscessus. Interestingly, we observed that while A. annua is not bactericidal, it inhibits growth of M. abscessus, highlighting the potential of this plant in combinatory therapies to treat M. abscessus infections. Conclusion: Our results indicate that Artemisia extracts have an enormous potential for treatment of TB and M. abscessus infections, and that these plants contain bactericidal compounds in addition to AN. Combination of extracts with existing antibiotics may not only improve treatment outcomes but also reduce the emergence of resistance to other drugs.
Applied and Environmental Microbiology, Dec 1, 1984
Evidence is presented here that axenic cultures of Chlorella, Scenedesmus, Coelastrum, and Chloro... more Evidence is presented here that axenic cultures of Chlorella, Scenedesmus, Coelastrum, and Chlorococcum spp. evolve N20 when grown on NO2, showing that the Chlorophyceae are a source of N20 in aquatic systems. Nitrous oxide (N20) is an intermediate in denitrification and a by-product of both nitrification and dissimilatory nitrogen oxide reduction (3, 18). The extent of the global source and pool of N20 is uncertain and especially controversial in aquatic systems (5, 7, 17). Recognition of new, widespread biological sources of N20 affects current theories of the global N20 balance. This report shows that the Chlorophyceae evolve N20 when grown on N02. These data show that the green algae are a previously unrecognized source of N20-Cells from actively growing axenic cultures of chlorellae in BG-11 medium (1) and of other species in MBM medium (16) (in air plus 1% CO2 at 25 + 2°C, under continuous irradiation of 8 to 11.3 W m-2 by Cool White [General Electric] fluorescent lights) were harvested by centrifugation, washed three times, and resuspended in the same volume of identical medium without any source of combined nitrogen. After 18 h, the cells were harvested by centrifugation. Portions of the thick slurry were suspended in 3 ml of the appropriate growth medium with and without NaNO2 (1.2 to 3.0 g
bioRxiv (Cold Spring Harbor Laboratory), Jul 25, 2022
The SARS-CoV-2 (COVID-19) global pandemic continuous to infect and kill millions while rapidly ev... more The SARS-CoV-2 (COVID-19) global pandemic continuous to infect and kill millions while rapidly evolving new variants that are more transmissible and evading vaccine-elicited antibodies. Artemisia annua L. extracts have shown potency against all previously tested variants. Here we further queried extract efficacy against omicron and its recent subvariants. Using Vero E6 cells, we measured the in vitro efficacy (IC50) of stored (frozen) dried-leaf hot-water A. annua L. extracts of four cultivars (A3, BUR, MED, and SAM) against SARS-CoV-2 variants: original WA1 (WT), BA.1.1.529+R346K (omicron), BA.2, BA.2.12.1, and BA.4. IC50 values normalized to the extract artemisinin (ART) content ranged from 0.5-16.5 µM ART. When normalized to dry mass of the extracted A. annua leaves, values ranged from 20-106 µg. Although IC50 values for these new variants are slightly higher than those reported for previously tested variants, they were within limits of assay variation. There was no measurable loss of cell viability at leaf dry weights ≤50 µg of any cultivar extract. Results continue to indicate that oral consumption of A. annua hot-water extracts (tea infusions) could potentially provide a cost-effective approach to help stave off this pandemic virus and its rapidly evolving variants.
Journal of Ethnopharmacology, Mar 1, 2021
Ethnopharmacological relevanceArtemisia annua has a long history of use in Southeast Asia where i... more Ethnopharmacological relevanceArtemisia annua has a long history of use in Southeast Asia where it was used to treat “fever” and A. afra has a similar history in southern Africa. Since their discovery, A. annua use, in particular, has expanded globally with millions of people using the plant in therapeutic tea infusions, mainly to treat malaria.Aim of the StudyIn this study, we used in vitro studies to query if and how A. annua and A. afra tea infusions being used across the globe affect asexual Plasmodium falciparum parasites, and their sexual gametocytes.Materials and MethodsP. falciparum NF54 was grown in vitro, synchronized, and induced to form gametocytes using N-acetylglucosamine. Cultures during asexual, early, and late stage gametocytogenesis were treated with artemisinin, methylene blue, and A. annua and A. afra tea infusions (5g DW/L) using cultivars that contained 0-283 μM artemisinin. Asexual parasitemia and gametocytemia were analyzed microscopically. Gametocyte morphology also was scored. Markers of early (PfGEXP5) and late stage (Pfs25) gametocyte gene expression also were measured using RT-qPCR.ResultsBoth A. annua and A. afra tea infusions reduced gametocytemia in vitro, and the effect was mainly artemisinin dependent. Expression levels of both marker genes were reduced and also occurred with the effect mainly attributed to artemisinin content of four tested Artemisia cultivars. Tea infusions of both species also inhibited asexual parasitemia and although mainly artemisinin dependent, there was a weak antiparasitic effect from artemisinin-deficient A. afra.ConclusionsThese results showed that A. annua and to a lesser extent, A. afra, inhibited parasitemia and gametocytemia in vitro.
Frontiers in Plant Science, Sep 18, 2020
Editorial on the Research Topic Artemisinin-From Traditional Chinese Medicine to Artemisinin Comb... more Editorial on the Research Topic Artemisinin-From Traditional Chinese Medicine to Artemisinin Combination Therapies; Four Decades of Research on the Biochemistry, Physiology, and Breeding of Artemisia annua The 2015 Nobel Prize in Physiology or Medicine was awarded to Tu Youyou for her "discoveries concerning a novel therapy against malaria". Educated in pharmaceutical sciences, Tu was recruited to Chinese military research Program 523, with the aim of finding new drugs for the treatment of malaria. A malaria epidemic during the Vietnam War had led Ho Chı́Minh, the Prime Minister of North Vietnam, to request medical help from China. In response, Chairman Mao approved Project 523, which involved over 500 scientists, military personnel, and medical practitioners and ran from 1967 to 1980. Whilst reviewing written records of traditional Chinese medicine, Tu noticed a mention of Qinghao (Artemisia annua) for alleviation of malaria fevers in Ge Hong's "A handbook of prescriptions for emergencies", which has been dated to around 317-420 A.D. She next found that an ethyl ether extract from A. annua leaves strongly inhibited malaria, leading Tu and two other members of her team to test the Qinghao plant extract for safety and side-effects on themselves. In 1972, Tu´s team obtained the pure active substance from this extract and determined its chemical structure, naming it as qinghaosu, or artemisinin, as it became more commonly known in the West. A series of chemical derivatives of artemisinin were subsequently developed by Project 523, including dihydroartemisinin, artemether, and artesunate. These compounds have become part of the artemisinin combination therapies (ACTs), currently the World Health Organisation (WHO)-recommended first-line drugs to combat malaria. Almost fifty years after Tu´s discovery, malaria still poses a global threat, with an estimated 228 million cases occurring worldwide in 2018 causing 405,000 deathstwo thirds of them among children under 5 years old in sub-Saharan Africa (World malaria report, 2019). The introduction of ACTs (it is estimated that 3 billion treatment courses have been procured worldwide between 2010
Acta horticulturae, Aug 1, 1996
Phytomedicine, 2019
Background: Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer with poor progno... more Background: Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer with poor prognosis. Artemisinin (AN), produced naturally in Artemisia annua L., has anti-cancer activity. Artemisinin delivered as dried leaf Artemisia (DLA) showed efficacy against malaria in rodents and humans. Hypothesis/Purpose: DLA is posited as being at least as efficacious as artesunate (AS) in its ability to induce cytotoxicity in NSCLC cells and inhibit tumor growth in a NSCLC xenograft murine model. Study Design: Three NSCLC cell lines were used, a non-cancerous human fibroblast line, and xenograft murine models to compare efficacy of artemisinin delivered p.o. via DLA, DLA extracts (DLAe), and AS. Methods: DLAe was compared to AS using NSCLC cell lines A549, H1299 and PC9 as well as non-cancerous human dermal fibroblasts (HDF) CCD-1108Sk line. Cell viability, cell migration and cell cycle were compared for AS and DLAe. Westerns measured activated caspases 3, 8 and 9 to determine involvement of intrinsic and/or extrinsic apoptotic pathways. Xenograft murine models of A549 and PC9 cells were used to measure tumor growth inhibition by AS or DLA, with tumor volume the primary endpoint. Results: Both DLAe and AS suppressed A549, H1299 and PC9 cell viability with no inhibition of non-cancerous HDF CCD-1108Sk cells. Caspases-3,-8 and-9 were activated, suggesting cell death was stimulated through both intrinsic and/or extrinsic apoptotic pathways. Both drugs induced G2/M or mitotic arrest in PC9 and H1299 cells, and DLAe induced G1 arrest in A549 cells. AS and DLAe induced DNA damage as double stranded breaks evidenced by phosphorylation of histone H2AX. DLAe inhibited migration of PC9 and A549 cells. In A549 xenografted animals, p.o. AS and DLA inhibited relative tumor growth by 40% and 50%, respectively, compared to controls. AS was ineffective at inhibiting PC9-induced tumor growth, but DLA inhibited relative tumor growth by ~50% compared to controls. Conclusion: This is the first study demonstrating efficacy of DLA and mechanistic differences of DLAe vs. AS, against NSCLC cells. Compared to AS, DLA possesses qualities of a novel therapeutic for patients with NSCLC.
Nitrous oxide (N/sub 2/O) is an intermediate in denitrification and a by-product of both nitrific... more Nitrous oxide (N/sub 2/O) is an intermediate in denitrification and a by-product of both nitrification and dissimilatory nitrogen oxide reduction. The extent of the global source and pool of N/sub 2/O is uncertain and especially controversial in aquatic systems. Recognition of new, widespread biological sources of N/sub 2/O affects current theories of the global N/sub 2/O balance. Evidence is presented here that axenic cultures of Chlorella, Scenedesmus, Coelastrum, and Chlorococcum spp. evolve N/sub 2/O when grown on NO/sub 2//sup -/, showing that the Chlorophyceae are a source of N/sub 2/O in aquatic systems. 18 references, 2 tables.
Planta Medica, Jun 1, 1992
Planta, Jul 15, 2021
Main conclusion This review analyses the most recent scientific research conducted for the purpos... more Main conclusion This review analyses the most recent scientific research conducted for the purpose of enhancing artemisinin production. It may help to devise better artemisinin enhancement strategies, so that its production becomes cost effective and becomes available to masses.
Social Science Research Network, 2022
Journal of Ethnopharmacology, Feb 1, 2022
Ethnopharmacological relevance: For millennia, Artemisia annua L. was used in Southeast Asia to t... more Ethnopharmacological relevance: For millennia, Artemisia annua L. was used in Southeast Asia to treat "fever". This medicinal plant is effective against multiple pathogens and is used by many global communities as a source of artemisinin derivatives that are first-line drugs to treat malaria caused by Plasmodium parasites. Aim of the study: The SARS-CoV-2 (Covid-19) global pandemic has killed millions and evolved numerous variants, with delta being the most transmissible to date and causing breakthrough infections of vaccinated individuals. We further queried the efficacy of A. annua cultivars against new variants. Materials and methods: Using Vero E6 cells, we measured anti-SARS-CoV-2 activity of dried-leaf hot-water A. annua L. extracts of four cultivars, A3, BUR, MED, and SAM, to determine their efficacy against five infectious variants of the virus: alpha (B.1.1.7), beta (B.1.351), gamma (P.1), delta (B.1.617.2), and kappa (B.1.617.1). Results: In addition to being effective against the original wild type (WT) WA1, A. annua cultivars A3, BUR, MED, and SAM were also potent against all five variants. IC 50 and IC 90 values based on measured artemisinin content ranged from 0.3 to 8.4 μM and 1.4-25.0 μM, respectively. The IC 50 and IC 90 values based on dried leaf weight (DW) used to make the tea infusions ranged from 11.0 to 67.7 μg DW and 59.5-160.6 μg DW, respectively. Cell toxicity was insignificant at a leaf dry weight of ≤50 μg in the extract of any cultivar. Conclusions: Results suggest that oral consumption of A. annua hot-water extracts (tea infusions) could potentially provide a cost-effective therapy to help stave off the rapid global spread of these variants, buying time for broader implementation of vaccines.
Springer eBooks, 2016
Plant molecular farming depends on a diversity of plant systems for production of useful recombin... more Plant molecular farming depends on a diversity of plant systems for production of useful recombinant proteins. These proteins include protein biopolymers, industrial proteins and enzymes, and therapeutic proteins. Plant production systems include microalgae, cells, hairy roots, moss, and whole plants with both stable and transient expression. Production processes involve a narrowing diversity of bioreactors for cell, hairy root, microalgae, and moss cultivation. For whole plants, both field and automated greenhouse cultivation methods are used with
Journal of Ethnopharmacology, Nov 1, 2022
bioRxiv (Cold Spring Harbor Laboratory), Sep 8, 2021
Ethnopharmacological relevance For millennia in Southeast Asia, Artemisia annua L. was used to tr... more Ethnopharmacological relevance For millennia in Southeast Asia, Artemisia annua L. was used to treat "fever". This medicinal plant is effective against numerous infectious microbial and viral diseases and is used by many global communities as a source of artemisinin derivatives that are first-line drugs to treat malaria. Aim of the Study The SARS-CoV-2 (Covid-19) global pandemic has killed millions and evolved numerous variants, with delta being the most transmissible to date and causing breakthrough infections of vaccinated individuals. We further queried the efficacy of A. annua cultivars against new variants. Materials and Methods .
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Papers by Pamela Weathers