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Biotechnological Studies of Medicinal Plants to Enhance Production of Secondary Metabolites under Environmental Pollution
Published in Azamal Husen, Environmental Pollution and Medicinal Plants, 2022
In addition to providing food, plants act as repositories of various chemical compounds exhibiting therapeutic potential. The World Health Organization has listed 21,000 plants having medicinal properties, of which India accounts for almost 2,500 plant varieties (Shukla et al. 2019; Pundarikakshudu and Kanaki 2019). Secondary metabolites are synthesized in plants via various metabolic pathways, such as acetate-malonate, phenylpropanoid, 2-C-methyl-d-erythritol-4-phosphate, mevalonate, glucose, and amino acid pathways, and environmental factors can also act as inducers for their production in plants (Gonçalves and Romano 2018; Shitan 2016) They are responsible for the medicinal properties of plants and also have a significant role in the survival of plants during environmental stress (Kliebenstein 2013). These plant-derived secondary metabolites have been used for the prevention and treatment of diseases for ages, due to their antifungal, antiviral, antidiabetic, antioxidant, immune-modulatory, hepato-protective, and reno-protective properties (Rasool Hassan 2012; Ghorbanpour et al. 2017).
The Widening Panorama of Natural Products Chemistry in Brazil
Published in Luzia Valentina Modolo, Mary Ann Foglio, Brazilian Medicinal Plants, 2019
Maria Fátima das Graças Fernandes da Silva, João Batista Fernandes, Moacir Rossi Forim, Michelli Massaroli da Silva, Jéssica Cristina Amaral
The sesqui-, di- and triterpenes appear to be common in Brazilian plants. During the last few years several accounts have been published on the biosynthesis of terpenes. The literature clearly has shown that all compounds of the family are derived from the two building blocks isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMAPP) and are biosynthesized either by the mevalonate (MVA) or the 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway (Figure 3.13). Nevertheless, no studies of the biosynthesis of this class have apparently been reported in Brazilian plants. Until recently the only work in this series is due to Maysa Furlan and her colleagues, who showed that enzymatic extracts obtained from leaves and/or root bark of Maytenus aquifolium (Celastraceae) and Salacia campestris (Hippocrateaceae) displayed cyclase activity with conversion of the substrate oxidosqualene to the triterpenes, 3-friedelanol and friedelin. In addition, administration of (±)5-3H mevalonolactone in leaves of M. aquifolium seedlings produced radio labeled friedelin in the leaves, twigs and stems, while the root bark accumulated labeled maytenin and pristimerin (89). These experiments indicated that the triterpenes once biosynthesized in the leaves are translocated to the root bark and further transformed to the quinonemethide triterpenoids (Corsino et al., 2000).
Biosynthetic Pathway of Artemisinin
Published in Tariq Aftab, M. Naeem, M. Masroor, A. Khan, Artemisia annua, 2017
The other pathway, the non-mevalonate pathway (MEP), to IPP begins with pyruvate and occurs in the plastid with no mevalonate intermediate. The first key, regulatory, step toward the synthesis of terpenes is the synthesis of 1-deoxy-D-xylulose-5-phosphate (DXP) via 1-deoxy-D-xylulose-5-phosphate synthase (DXS). DXP is then converted to 2-C-methyl-D-erythritol-4-phosphate via 1-deoxy-D-xylulose-5-phosphate reductoisomerase (DXR). Several subsequent steps synthesize the plastid pool of IPP (Rohmer et al., 1996).
PD-1 checkpoint blockade enhances adoptive immunotherapy by human Vγ2Vδ2 T cells against human prostate cancer
Published in OncoImmunology, 2021
Mohanad H. Nada, Hong Wang, Auter J. Hussein, Yoshimasa Tanaka, Craig T. Morita
Stimulation of Vγ2Vδ2 T cells by this wide variety of microbial pathogens is through their TCRs. Unlike conventional CD8 and CD4 αβ T cells that respond to peptides presented by MHC class I and class II molecules, Vγ2Vδ2 TCRs are triggered by shared intracellular isoprenoid metabolites and other phosphorylated metabolites also commonly termed as phosphoantigens. Foreign phosphorylated metabolites, such (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate in the 2-C-methyl-D-erythritol 4-phosphate isoprenoid synthesis pathway, or overproduced endogenous isoprenoid metabolites, such as isopentenyl pyrophosphate (IPP) in the mevalonate pathway,4 are sensed by the intracellular B30.2 domain of BTN3A1.5,6 Binding is signaled to its extracellular domain through an unknown mechanism and, in conjunction with BTN2A1,7,8 leads to recognition by the Vγ2Vδ2 TCR and T cell activation. This sensor system allows Vγ2Vδ2 T cells to surveil the cytoplasm of cells and eliminate those with aberrant isoprenoid metabolism because of mutagenesis or infection.
Antiproliferative and cytotoxic effects of sesquiterpene lactones isolated from Ambrosia artemisiifolia on human adenocarcinoma and normal cell lines
Published in Pharmaceutical Biology, 2022
Balázs Kovács, Nikoletta Szemerédi, Norbert Kúsz, Tivadar Kiss, Boglárka Csupor-Löffler, Yu-Chi Tsai, Bálint Rácz, Gabriella Spengler, Dezső Csupor
Eight compounds were isolated from the MeOH extract of the aerial parts of A. artemisiifolia and based on HR-MS and NMR experiments their structures were identified as the sesquiterpenes psilostachyin C (1), acetoxydihydrodamsin (2), peruvin (3), psilostachyin (4), 1′-noraltamisin (5), psilostachyin B (6), 1,10-dihydro-1′-noraltamisin (7) and the flavonoid axillarin (8). After comparing NMR data of 1,10-dihydro-1′-noraltamisin (7) with those found in the literature, it was realized that this compound was obtained for the first time from the plant. It belongs to a rare class of seco-psilostachyinolides bearing an open ring system. It can be hypothesized that the biosynthesis of this class of seco derivatives takes place in two independent pathways: the mevalonic acid (MVA) pathway in the cytoplasm or the 2-C-methyl-d-erythritol-4-phosphate (MEP) pathway in the plastids (Bick and Lange 2003). The precursor in both cases, 2e,6e-farnesyl pyrophosphate (FPP), results from the addition of a molecule of IPP onto GPP. The skeleta of this open ring system arise from the cyclodecadiene-type product of the cyclization of FPP, or of its geometrical isomer at C-2 (2z,6e-FPP), or of nerolidyl pyrophosphate, by nucleophilic attack on the distal double bond which leads to the germacradienyl cation, from which may arise also the other lactone skeletal types (Jean 1999). Until now just a few of this type of seco derivatives were reported in the literature from the genus Ambrosia. 1′-Noraltamisin (5) was reported only from a Mexican population (collected in North Zacatecas) of Ambrosia confertiflora DC (Delgado et al. 1988). Structurally similar sesquiterpene lactones, altamisin from A. peruviana (Central American collection) (Borges et al. 1978) and altamisic acid from A. tenuifolia (collection form North Central Argentina), were also reported (Oberti et al. 1986). From a Yugoslavian collection of A. artemisiifolia, Stefanović et al (1987) isolated 4-oxo-3,4-seco-ambrosan-6,12-olide-3-oic acid; the same compound was also found by Taglialatela-Scafati et al. (2012) from an Italian plant sample.