Exploring the potential of omics technologies in medicinal plant research: a review in Colombia / Explorando el potencial de las tecnologías ómicas en la investigación de plantas medicinales: una revisión en Colombia

This review presents advances in the implementation of high - throughput se quencing and its application to the knowledge of medicinal plants. We conducted a bibliographic search of papers published in PubMed, Science Direct, Google Scholar, Scopus, and Web of Science databases and analyzed the obtained data using VOSviewer (versi on 1.6.19). Given that medicinal plants are a source of specialized metabolites with immense therapeutic values and important pharmacological properties, plant researchers around the world have turned their attention toward them and have begun to examine t hem widely. Recent advances in sequencing technologies have reduced cost and time demands and accelerated medicinal plant research. Such research leverages full genome sequencing, as well as RNA (ribonucleic acid) sequencing and the analysis of the transcr iptome, to identify molecular markers of species and functional genes that control key biological traits, as well as to understand the biosynthetic pathways of bioactive metabolites and regulatory mechanisms of environmental responses. As such, the omics ( e.g., transcriptomics, metabolomics, proteomics, and genomics, among others) have been widely applied within the study of medicinal plants, although their usage in Colombia is still few and, in some areas, scarce. (185)

El extracto de cloroformo (CE) y las fracciones obtenidas de las raíces de Aldama arenaria se evaluaron para determinar su actividad antiproliferativa in vitro contra 10 líneas ce lulares tumorales humanas [leucemia (K - 562), mama (MCF - 7), ovario que expresa un fenotipo resistente a múltiples fármacos (NCI/ADR - RES), melanoma (UACC - 62), pulmón (NCI - H460), próstata (PC - 3), colon (HT29), ovario (OVCAR - 3), glioma (U251) y riñón (786 - 0)]. CE presentó actividad antiproliferativa débil a moderada (log GI 50 medio 1.07), mientras que las fracciones 3 y 4, enriquecidas con diterpenos de tipo pimarane [ent - pimara - 8 (14), ácido 15 - dien - 19 - oico y ent - 8(14),15 - pimaradien - 3 ß - ol], presentaron activid ad moderada a potente para la mayoría de las líneas celulares, con un log GI 50 medio de 0.62 y 0.59, respectivamente. Los resultados mostraron una acción antiproliferativa in vitro prometedora de las muestras obtenidas de A. arenaria , con los mejores resul tados para NCI/ADR - RES, HT29 y OVCAR - 3, y valores de TGI que van desde 5.95 a 28.71 µg.mL - 1, demostrando que los compuestos de esta clase pueden ser prototipos potenciales para el descubrimiento de nuevos agentes terapéuticos

Structurally diverse (9ß-H)-pimarane derivatives with six frameworks from the leaves of Icacina oliviformis and their cytotoxic activities.

Thirteen previously undescribed (9ß-H)-pimarane derivatives, icacinolides A-G (1-7) and oliviformislactones C-H (8-13), together with four known analogs (14-17), were isolated from the leaves of Icacina oliviformis. Their structures were constructed by extensive spectroscopic analysis, 13C NMR-DP4+ analysis, ECD calculation, single-crystal X-ray diffraction, and chemical methods. These structurally diverse isolates were classified into six framework types: rearranged 3-epi-17-nor-(9ß-H)-pimarane, rearranged 17-nor-(9ß-H)-pimarane, 16-nor-(9ß-H)-pimarane, 17-nor-(9ß-H)-pimarane, 17,19-di-nor-(9ß-H)-pimarane, and (9ß-H)-pimarane. Among them, compounds 1, 5, and 7 were the first examples of three rearranged 3-epi-17-nor-(9ß-H)-pimaranes featuring a unique (11S)-carboxyl-9-oxatricyclo[5.3.1.02,7]dodecane motif with contiguous stereogenic centers, whereas their C-3 epimers, compounds 2-4 and 6 were the second examples of four rearranged 17-nor-(9ß-H)-pimaranes. Additionally, compounds 8 and 12/13 represented the second examples of a 16-nor-(9ß-H)-pimarane and two 17,19-di-nor-(9ß-H)-pimaranes, respectively. In cytotoxic bioassay, compound 2 exhibited significant cytotoxic against HT-29 with IC50 values of 7.88 µM, even stronger than 5-fluorouracil, and 15 showed broad-spectrum cytotoxic activities against HepG2, HT-29, and MIA PaCa-2 with IC50 values of 11.62, 9.77, and 4.91 µM, respectively. Meanwhile, a preliminary structure-activity relationship suggested that 3,20-epoxy, 6,19-lactone, 2-OH, 7-OH, and 8-OH in (9ß-H)-pimarane derivatives might be active groups, whereas ring C aromatization may decrease the cytotoxic activities.

Diterpenoids from Euphorbia lactea and their anti-HIV-1 activity.

Nine undescribed diterpenoids, euphlactenoids A-I (1-9), including four ingol-type diterpenoids (1-4) with a 5/3/11/3-tetracyclic framework and five ent-pimarane-type diterpenoids (5-9), together with thirteen known diterpenoids (10-22), were identified from the leaves and stems of Euphorbia lactea Haw. The structures and absolute configurations of compounds 1-9 were unequivocally elucidated on the basis of spectroscopic analysis, ECD calculations and single crystal X-ray diffraction. Compounds 3 and 16 showed anti-HIV-1 effects with IC50 values of 1.17 µM (SI = 16.54) and 13.10 µM (SI = 1.93), respectively.

Diverse diterpenoids from Callicarpa rubella Lindl. as natural inhibitors of macrophage foam cell formation.

Ten undescribed diterpenoids namely rubellawus E-N of structural types pimarane (1, 3-4), nor-abietane (2), nor-pimarane (5-6), isopimarane (7-9), and nor-isopimarane (10), along with eleven known compounds, were isolated and identified from the aerial parts of Callicarpa rubella Lindl. The structures of the isolated compounds were confirmed by comprehensive spectroscopic analyses and quantum chemical computations. Pharmacologically, almost all the compounds exhibited a potential inhibitory effect on oxidized low-density lipoprotein-induced macrophage foam cell formation, which suggests that these compounds may be promising candidates in the treatment of atherosclerosis.

New 21-nordammarane saponins with anti-inflammatory and cytotoxic activities from Lavigeria macrocarpa Oliv.

Chemical investigation of the ethanol extract from the stems and roots of the medicinal plant Lavigeria macrocarpa led to the isolation and structure elucidation of three previously unreported 21-nordammarane-type saponins namely 6α,27-dihydroxy-3,20-dioxo-21-nordammar-24-(Z)-ene 27-O-[α-L-rhamnopyranosyl-(1→2)-ß-D-glucopyranoside] (1), 6α,27-dihydroxy-3-oxo-21-nordammar-24-(Z)-ene 27-O-ß-D-glucopyranoside (2), and 2α,3ß,6α,27-tetrahydroxy-21-nordammar-24-(Z)-ene 27-O-ß-D-glucopyranoside (3) trivially named lavigemacrocarposide A-C, along with eight known secondary metabolites. Acid hydrolysis of lavigemacrocarposide A yielded a new prosapogenin namely 6α,27-dihydroxy-3,20-dioxo-21-nordammar-24-(Z)-ene 27-O-ß-D-glucopyranoside (1a) and the previously unreported artefactual aglycones 1b and 1c. Their structures were elucidated by spectroscopic analyses including mass spectrometry, 1D and 2D NMR as well as chemical evidence. The EtOH extract, some isolated compounds as well as the prosapogenin (1a) and compounds 1b and 1c were evaluated for anti-inflammatory and cytotoxic activity. Icacine (5) exhibited a significant cytotoxicity against both HeLa and MCF-7 cell lines with an IC50 value of 0.78 µg/mL. All the tested compounds showed more that 50% inhibition of NO production, except for 1 and 2.

New diterpenoids and phenolic amides from Icacina mannii Oliv.

Fourteen undescribed compounds including five neoclerodanes (1-5), three labdanes (12-14), three pimarane (15-17) derivatives, one carbamate (24) and two clovamide-type amides (25 and 26), along with twenty-two known compounds (6-11, 18-23 and 27-36) were isolated from the tuber and stem of Icacina mannii. Their structures were elucidated by 1D and 2D NMR and HR-ESI-MS data analysis, and by comparing their NMR data with those of the literature.

ent-Pimarane Diterpenes from the Aerial Parts of Siegesbeckia pubescens.

Five new ent-pimarane diterpenes (1-5) and five known analogs (6-10) were isolated from the aerial parts of Siegesbeckia pubescens. Their structures, including absolute configurations, were determined by comprehensive spectroscopic methods especially 1D and 2D NMR and quantum chemical electronic circular dichroism calculations. All the isolated compounds were evaluated for their cytotoxicity against human BT549, A549 and H157 cancer cell lines. Among them, compounds 1 and 2 showed mild cytotoxicity against lung cancer cell lines H157 with IC50 values of 16.35±2.59 and 18.86±4.83 µM, respectively.

Methyl 2-naphthoates with anti-inflammatory activity from Morinda officinalis.

Chemical fractionation of the EtOH extract of the roots of a traditional Chinese herb, Morinda officinalis, afforded an array of methyl 2-naphthoate derivatives (1-9) including four pairs of enantiomers (1-4), two pimarane diterpenes and two ursane triterpenoids. Among them, eight compounds (1a/1b-3a/3b, 11 and 13) were reported in the current work for the first time. The structures of the new compounds, including their absolute configurations, were defined by spectroscopic analyses in combination with quantum chemical electronic circular dichroism (ECD) and gauge-independent atomic orbital (GIAO) NMR calculations. All the isolates were evaluated for their inhibitory effect on nitric oxide (NO) production induced by lipopolysaccharide (LPS) in murine RAW264.7 macrophage cells, and the enantiomers 1a and 3b exhibited moderate activity with IC50 values of 41.9 and 26.2 µM. Meanwhile, compound 3b also dose-dependently inhibited the secretion of two pro-inflammatory cytokines TNF-α and IL-6 in the same cell model.

Pimarane Diterpenes from Fungi.

Pimarane diterpenes are a kind of tricyclic diterpene, generally isolated from plant and fungi. In nature, fungi distribute widely and there are nearly two to three million species. They provide many secondary metabolites, including pimarane diterpenes, with novel skeletons and bioactivities. These natural products from fungi have the potential to be developed into clinical medicines. Herein, the structures and bioactivities of 197 pimarane diterpenes are summarized and the biosynthesis and pharmacological researches of pimarane diterpenes are introduced. This review may be useful improving the understanding of pimarane diterpenes from fungi.

A Synthetic View on Momilactones and Related 9ß-H Pimarane Skeleton Diterpenoids.

Allelochemicals are secondary metabolites produced from plants and used to prevent and control the invasion of other plants and microorganisms, with broad application prospects in crop protection. Structurally, momilactones belong to 9ß-H pimarane diterpenoids, one of rice's significant allelochemicals with anti-weeds and antibacterial activity. Rare studies have been reported with the synthesis challenges of the unique 9ß-H pimarane skeleton. Hence, synthetic strategies of momilactones and related 9ß-H pimarane skeleton are reviewed from 1984 to 2021.

Plantas medicinales utilizadas en la región de Teziutlán, Puebla, México / Medicinal plants used in the region of Teziutlán, Puebla, México

The objective of this work was to collect information on the curative use of plants in the municipality of Teziutlán, Puebla through semi-structured interviews. Thus, 78 plants used for medicinal purposes were identified, of which 40 are native to Mexico and 38 introduced; The value of use (UV) of each one and the Informant's Consensus Factor (FCI) of 10 categories of diseases were calculated. The five most frequently used plants are Ruta chalepensis L., Rosmarinus officinalis, Arnica montana, Loeselia mexicana (Lam.) Brandegee and Sambucus cerulea var., Neomexicana, which underwent a chemical and pharmacological review. On the other hand, the most frequent preparations are infusion and decoction, using mainly leaves (49.34%) and flowers (19.51%). It is concluded that the inhabitants of Teziutlán have a fairly homogeneous ethnomedical knowledge, setting the standard for research on its pharmacological properties.

El objetivo del presente trabajo fue recopilar información sobre el uso curativo de las plantas del municipio de Teziutlán, Puebla por medio de entrevistas semiestructuradas. Así, se identificaron 78 plantas utilizadas con fines medicinales, de las cuales 40 son propias de México y 38 introducidas; se calculó el valor de uso (UV) de cada una y el Factor de Consenso del Informante (FCI) de 10 categorías de padecimientos. Las cinco plantas utilizadas con mayor frecuencia son Ruta chalepensis L., Rosmarinus officinalis, Arnica montana, Loeselia mexicana (Lam.) Brandegee y Sambucus cerulea var., neomexicana, a las que se les hizo una revisión química y farmacológica. Por otro lado, las preparaciones más frecuentes son infusión y decocción, utilizando principalmente hojas (49.34 %) y flores (19.51 %). Se concluye que los habitantes de Teziutlán cuentan con un conocimiento etnomédico bastante homogéneo, dando la pauta para investigaciones sobre sus propiedades farmacológicas.

Pimarane, abietane, and labdane diterpenoids from Euphorbia pekinensis Rupr. and their anti-tumor activities.

Chemical investigation of the roots of Euphorbia pekinensis Rupr. led to the isolation of five undescribed labdane diterpenoids "(4S, 5S, 9R, 10S, 13R)-18-O-galloyl-labda-8(17), 14(15)-dien-13-ol; (4S, 5S, 9R, 10S, 13R)-13-hydroxy-labda-8(17), 14(15)-dien-18-one; (4S, 5S, 9R, 10S, 13R)-18-O-acetyl-labda-8(17), 14(15)-dien-13-ol; (4S, 5S, 9R, 10S)-labda-8(17), 13(16), 14(15)-trien-18-ol; (5R, 6R, 9R, 10S, 13R)-labda-8(17), 14(15)-dien-6,13-diol", two undescribed pimarane diterpenoids "(2R, 5S, 9R, 10S, 12R, 13R)-2,12-dihydroxy-isopimara-7,15-dien-3-one; (5S, 9R, 10S, 12R, 13R)-2, 12-dihydroxy-isopimara-1, 7, 15-trien-3-one)", together with nine known diterpenoids, including three pimarane-type "(3ß,11α,13α)-3,11-dihydroxypimara-7,15-diene-2,12-dione; (11R, 12S)-2,11,12-trihydroxy-ent-isopimara-1,7,15-trien-3-one; isopimara-7,15-dien-3ß-ol)", five abietane-type "helioscopinolide A-C; helioscopinolide E; helioscopinolide I″, and one lathyrane-type "jolkinol B". The structures of these compounds were elucidated by analysis of HRESIMS, 1D NMR, 2D NMR, and X-ray diffraction. These sixteen compounds were evaluated for cytotoxic activity in vitro against three human cancer cell lines, U-937, LOVO, and K-562. Jolkinol B exhibited IC50 of 3.60 µM and 8.44 µM against U-937 and LOVO cell lines, (4S, 5S, 9R, 10S, 13R)-18-O-galloyl-labda-8(17), 14(15)-dien-13-ol displayed IC50 of 5.92 µM against U-937 cell lines, isopimara-7,15-dien-3ß-ol showed IC50 of 0.87 µM against K-562 cell lines.

Sigesbeckia K and L, two new diterpenoids from Sigesbeckia glabrescens with anti-inflammatory activity.

A chemical investigation of Sigesbeckia glabrescens Makino identified four compounds. On the basis of spectroscopic data, they were determined to be ent-pimarane-type diterpenoids and their analogues, among which were two previously undescribed compounds, Sigesbeckia K (1) and Sigesbeckia L (2). The anti-inflammatory effects of these compounds were evaluated by testing their inhibition of LPS-induced NO production in BV2 microglial cells, which revealed potential inhibitory effects with IC50 value at 62.56 µM and compared with the positive control minocycline (IC50 32.84 µM).

A novel ent-pimarane-type diterpenoid from Sigesbeckia glabrescens with anti-inflammatory activity.

A novel ent-pimarane-type diterpenoid, sigesbeckia J (1), along with two known diterpenoids, siegesbeckia acid (2) and ent-18-acetoxy-16R,17-dihydroxykauran-19-oic acid (3), were isolated from the aerial parts of Sigesbeckia glabrescens Makino. Their chemical structures were elucidated based on extensive spectroscopic interpretation. The absolute configuration of ent-pimarane-type diterpenoid (1) was determined by comparing experimental and calculated ECD spectra. Compared with the positive control minocycline (IC50 32.84 µM), compound 1 exhibited moderate cell growth anti-inflammatory activities in vitro by testing their inhibition of LPS-induced NO production in BV2 microglial cells, with IC50 value of 58.74 µM.

In vitro anti-trypanosomal potential of kaurane and pimarane semi-synthetic derivatives.

As part of the search for anti-trypanosomal agents, this work presents the production of sixteen derivatives. All of them were obtained from two natural diterpenes, one with kaurane skeleton (ent-kaurenoic acid) and other with a pimarane skeleton (ent-pimaradienoic acid). Then, the eighteen compounds were assayed against epimastigote form of Trypanosoma cruzi, with the derivatives showing increase of activity in relation to their precursors. Moreover, the most active derivative presented an IC50 <12.5 µM (estimated 0.8 µM), lower than Benznidazole (IC50 = 9.8 µM), used as control. The esterification of acid diterpenes showed to be an interesting way in the search for anti-trypanosomal agents.

3, 4-seco-Isopimarane and 3, 4-seco-pimarane diterpenoids from Callicarpa nudiflora.

A phytochemical investigation was carried out on the extract of a medicinal plant Callicarpa nudiflora, resulting in the characterization of five new 3, 4-seco-isopimarane (1-5) and one new 3, 4-seco-pimarane diterpenoid (6), together with four known compounds. The structures of the new compounds were fully elucidated by extensive analysis of MS, 1D and 2D NMR spectroscopic data, and time-dependent density functional theory (TDDFT) calculation of electronic circular dichroism (ECD) spectra, and DFT calculations for NMR chemical shifts and optical rotations.

Sphaeropsidin A: A Pimarane Diterpene with Interesting Biological Activities and Promising Practical Applications.

Sphaeropsidin A (SphA) is a tetracyclic pimarane diterpene, first isolated as the main phytotoxin produced by Diplodia cupressi the causal agent of a severe canker disease of Italian cypress (Cupressus sempervirens L.). It was also produced, together with several analogues, by different pathogenic Diplodia species and other fungi and showed a broad array of biological activities suggesting its promising application in agriculture and medicine. The anticancer activity of SphA is very potent and cell specific. Recent studies have revealed its unique mode of action. This minireview reports the structures of SphA and its family of natural analogues, their biosynthetic origins, their fungal sources, and biological activities. The preparation of various SphA derivatives is also described as well as the results of structure-activity relationship (SAR) studies and on their potential practical applications.

Isolation and characterization of ent-pimarane diterpenoids from Sigesbeckia pubescens.

Five new ent-pimarane diterpenoids ent-16-nor-2-oxopimar-8(14)-ene-15,19-dial (1), ent-16-nor-2α,19-dihydroxypimar-8-en-15-al (2), 3-O-acetyldarutigenol (3), 19-O-acetylkirenol (4), ent-16-nor-3ß,15-dihydroxypimar-8(14)-ene (5) were isolated and characterized from the ethanol extract of Sigesbeckia pubescens. Their structures were elucidated on the basis of spectroscopic analysis. The absolute configuration of C-15 in compounds 3 and 4 was assigned using Snatzke's method. All these compounds were assessed for their anti-inflammatory potential by measuring the inhibitory effects on NO production in LPS-induced RAW 264.7 macrophage cells and compound 4 showed significantly inhibitory activity with IC50 value of 5.9 µM.

Diterpenoids and phenolic analogues from the roots of Aralia continentalis.

Two new compounds, including a nor-pimarane diterpenoid (continentanol, 1) and a phenolic derivative (aralianic acid, 2), along with the known diterpenoids (3-11), polyacetylenes (12-15), phenolic components (16-28), and phytosterols (29 and 30), were isolated from roots of Aralia continentalis. The structures of the new compounds were established by spectroscopic data interpretation, particularly HRESIMS, 1 D and 2 D NMR data including HSQC and HMBC. Also, those of the known compounds were identified by spectral comparison with those of the reported values.[Formula: see text].

3, 4-seco-Isopimarane and 3, 4-seco-pimarane diterpenoids from Callicarpa nudiflora / 中国天然药物

A phytochemical investigation was carried out on the extract of a medicinal plant Callicarpa nudiflora, resulting in the characterization of five new 3, 4-seco-isopimarane (1-5) and one new 3, 4-seco-pimarane diterpenoid (6), together with four known compounds. The structures of the new compounds were fully elucidated by extensive analysis of MS, 1D and 2D NMR spectroscopic data, and time-dependent density functional theory (TDDFT) calculation of electronic circular dichroism (ECD) spectra, and DFT calculations for NMR chemical shifts and optical rotations.