Heterocyclic Drugs from Plants
Rohit Dutt, Anil K. Sharma, Raj K. Keservani, Vandana Garg in Promising Drug Molecules of Natural Origin, 2020
This essential oil is extracted by hydrodistillation, another form of steam distillation (Bilia et al., 2014). In this form of distillation, the plant part is water-logged for a stipulated time and then heated. The heat of the distillation carries away the volatile materials (Zheljazkov et al., 2014). Some terpenoids are able to increase blood flow and to kill respiratory pathogens such as MRSA (methicillin-resistant staphylococcus aureus), the antibiotic-resistant bacteria responsible for many types of illness (Terpenes and the “Entourage Effect,” 2018). Artemisinin demonstrated very high potential against some bacteria and fungi. Two examples are C. albicans and A. fumigatus (Bilia et al., 2014). Another such experiment was done and extract showed efficacy against some periodontopathic microorganisms. A. actinomycetemcomitans, F. nucleatum subsp. animalis, F. nucleatum subsp. polymorphum, and P. intermedia are some of the microorganisms wherethe extract showed potency (Wan-Su, 2015). Most importantly, artemisinin, and its semi-synthetic derivatives are highly active commercially available drugs in treating malignant malaria, caused by Plasmodium falciparum.
Cultivation of Artemisia annua—The Environmental Perspective
Tariq Aftab, M. Naeem, M. Masroor, A. Khan in Artemisia annua, 2017
Bioactive secondary metabolites represent a wide range of different chemical compounds, but the three major classes are nitrogen-containing compounds, phenols, and terpenes. Artemisinin, produced by Artemisia annua L. (sweet wormwood, annual wormwood, sweet annie, sweet sagewort) belongs to the terpenes group. Artemisinin is a sesquiterpene lactone with an endoperoxide bridge (Liu et al., 1979), and is very bioactive against chloroquine-resistant strains of the malaria parasite Plasmodium falciparum (Klayman, 1985). Today, combination therapies containing artemisinin are recommended as the first-line treatment for malaria in 77 out of 80 countries and amounted to 311 million treatments worldwide in 2015 (WHO, 2015). The bioactivity of a plant-produced compound is two-sided: on one side, it has pharmaceutical benefits or can be useful in pest management; on the other side, its bioactivity can cause unwanted toxicity to beneficial non-target organisms. Just as anthropogenic pesticides and pharmaceuticals, plant-produced compounds can be toxic to both target and non-target organisms in the environment. In several cases, loss of bioactive secondary metabolites from plants to soil has been documented (Strobel et al., 2005; Gimsing and Kirkegaard, 2006; Hoerger et al., 2009; Zhang et al., 2011). When plants grow naturally in mixed vegetation, the load of individual secondary metabolites will usually be relatively low. This changes in intensely cultivated monocultures as the density of the toxin-producing plant species increases, and the plant variety may have been bred to produce even more of the desired bioactive secondary metabolite. In these dense monocultures and crops, large amounts of bioactive substances may potentially be released to the soil and water environments (Strobel et al., 2005; Gimsing and Kirkegaard, 2006; Hoerger et al., 2009; Carlsen et al., 2012). At present, total chemical synthesis (Abdin et al., 2003) or in vitro production of artemisinin is not economically feasible (Peplow, 2016), and cultivation of the plant is still the only cost-effective source. The cultivation of high-producing A. annua on a field scale, Pharmland (Figure 7.1), poses a risk of losing bioactive compound to the environment, where it might affect vulnerable organisms in the soil and/or leach into ground or surface waters.
Examples of single Chinese and botanical medicines derived from TCM
Raymond Cooper, Chun-Tao Che, Daniel Kam-Wah Mok, Charmaine Wing-Yee Tsang in Chinese and Botanical Medicines, 2017
The areas in the world most associated with malaria are shown in red in Figure 6.1. Two major drugs are employed in the fight against malaria and both originate directly from natural products: quinine from the bark of the cinchona tree found in South America and artemisinin from the leaves of Artemisia annua native to China. The latter discovery is particularly important as the effectiveness of drugs based solely on quinine has gradually diminished as the infecting parasites have developed resistance to the quinine-based drugs. Subsequently, artemisinin has become the treatment of choice for malaria. However, the World Health Organization (WHO) called for cessation of the single use of artemisinin preparations in 2006 in favor of combinations of artemisinin with another malarial drug to reduce the risk of the parasites developing resistance. Thus, artemisinin is usually combined with a synthetic derivative of quinine, known as chloroquine. This dual dose of the drugs reinforces one another in addressing malaria and has complementary roles; the former is fast acting while the latter reduces inflammation. However, it remains to be seen whether the strategy of combination therapy will be entirely successful in the management of malaria. More recently, this new and completely different antimalarial miracle drug, artemisinin, has been extracted from the leaves of Artemisia annua grown in China (Figure 6.2). The chemical structure of artemisinin possesses an unusual peroxide linkage, which is believed to be involved in the antimalarial effectiveness of the drug and may also account for its relatively rapid medical action compared to quinine. The WHO recognizes that artemisinin is very effective in the prevention and treatment of malaria even in cases where the parasite responsible is resistant to quinine. However, to avoid resistance during any artemisinin treatment, the WHO recommends a combination therapy of artemisinin and quinine derivatives, respectively.
Application of hot melt extrusion for improving bioavailability of artemisinin a thermolabile drug
Published in Drug Development and Industrial Pharmacy, 2018
C. Kulkarni, A. L. Kelly, T. Gough, V. Jadhav, K. K. Singh, A. Paradkar
Hot melt extrusion has been used to produce a solid dispersion of the thermolabile drug artemisinin. Formulation and process conditions were optimized prior to evaluation of dissolution and biopharmaceutical performance. Soluplus®, a low Tg amphiphilic polymer especially designed for solid dispersions enabled melt extrusion at 110 °C although some drug-polymer incompatibility was observed. Addition of 5% citric acid as a pH modifier was found to suppress the degradation. The area under plasma concentration time curve (AUC0–24h) and peak plasma concentration (Cmax) were four times higher for the modified solid dispersion compared to that of pure artemisinin.
Emerging artemisinin resistance in the border areas of Thailand
Published in Expert Review of Clinical Pharmacology, 2013
Kesara Na-Bangchang, Juntra Karbwang
Emergence of artemisinin resistance has been confirmed in Cambodia and the border areas of Thailand, the well-known hotspots of multidrug resistance Plasmodium falciparum. It appears to be spreading to the western border of Thailand along the Thai–Myanmar border, and will probably spread to other endemic areas of the world in the near future. This raises a serious concern on the long-term efficacy of artemisinin-based combination therapies, as these combination therapies currently constitute the last effective and most tolerable treatment for multidrug-resistant Plasmodium falciparum. Attempts have been made by a diverse array of stakeholders to prevent the emergence of new foci of artemisinin resistance, as well as to limit the spread of resistance to the original foci. The success in achieving this goal depends on effective integration of containment and surveillance programs with other malaria control measures, with support from both basic and operational research.
Artemisinin alleviates atherosclerotic lesion by reducing macrophage inflammation via regulation of AMPK/NF-κB/NLRP3 inflammasomes pathway
Published in Journal of Drug Targeting, 2020
Yan Jiang, Hongjiao Du, Xue Liu, Xi Fu, Xiaodong Li, Qian Cao
There is increasing evidence that atherosclerosis is the significant risk factor for cardiovascular diseases, which are the leading causes of morbidity and mortality worldwide. Artemisinin is a natural endoperoxides quiterpene lactone compound in Artemisia annua L with vasculoprotective effects. The primary aim of this study was to investigate whether artemisinin could be conferred an anti-atherosclerotic effect in high-fat diet (HFD)-fed ApoE–/– mice and explore the possible mechanism. We found that treatment with artemisinin (50 and 100 mg/kg) effectively ameliorated atherosclerotic lesions, such as foam cell formation, hyperplasia and fibrosis in the aortic intima. Atherosclerotic mice treated with artemisinin showed reduced inflammation by up-regulating adenosine 5′-monophosphate (AMP) activated protein kinase (AMPK) activation and by down-regulating nuclear factor-κB (NF-κB) phosphorylation and nod-like receptor family pyrin domain containing 3 (NLRP3) inflammasome expression in the aortas. In addition, artemisinin was found to promote AMPK activity in macrophages and its anti-inflammatory effect was neutralised by AMPK silence using specific siRNA. In conclusion, we demonstrate that artemisinin may protect the aortas from atherosclerotic lesions by suppression of inflammatory reaction via AMPK/NF-κB/NLRP3 inflammasomes signalling in macrophages.
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