The cytotoxic norditerpene dilactones of Podocarpus milanjianus and Podocarpus sellowii

The cytotoxic norditerpene dilactones nagilactone F and its new congener nagilactone G have been isolated from the bark constituents of Podocarpus milanjianus and Podocarpus sellowii. The diterpenes totarol, 19-oxototarol and macrophyllic acid were also isolated.     

Phenolic diterpenoids of some Podocarps

The woods of 10 species of the Podocarpaceae have variously yielded 12 phenolic diterpenoids. These include the Fijian members Dacrydium nidulum, Decussocarpus vitiensis, Podocarpus neriifolius and Dacrycarpus imbricatus, as well as Podocarpus gracilior, P. polystachus, P. sylvestris, P. gnidioides, Dacrydium comosum and D. falciforme.     

Norditerpene dilactones from Podocarpus saligna

Rimuene and nubigenol have been identified in Podocarpus saligna for the first time, and the structures of three new norditerpene dilactones, salignones K, L and M, isolated from this species have been elucidated.     

Lignan and norditerpene dilactone constituents of Podocarpus saligna

Thujaplicatin methyl ether and a new norditerpene dilactone named salignone I have been isolated from the roots of Podocarpus saligna and their structures determined by high field ¹H NMR and NOE difference spectroscopy.     

Terpenoids from the leaves of Podocarpus gracilior

Three new terpenoids, 2α,16-dihydroxy-4β-carboxy-O-β-d-glucopyranosyl-19-nor-totarol (1), nagilactone K (2), and 15-hydroxy phaseic acid (3), together with nine known compounds, were isolated from the leaves of Podocarpus gracilior. Their structures were determined by means of 1D and 2D NMR spectroscopy as well as by mass spectrometry analysis.     

Diterpenoids of Podocarpus nubigena

From the leaves and stems of Podocarpus nubigena Lindl. have been isolated rimuene, nagilactone-C, a new norditerpene. nubilactone-A (IV), daucosterin, sitosterol and cyanidin.     

Nubigenol: An α-hydroxydihydrochalcone from Podocarpus nubigena

The structure of nubigenol, a new chalcone from Podocarpus nubigena, has been identified as α,2,4,6,4′-pentahydroxydihydrochalcone (I).     

Inhibitory effect of Rhus verniciflua Stokes extract on human aromatase activity; butin is its major bioactive component

Rhus verniciflua Stokes has been used as a traditional herbal medicine in Asia. In this study, the effect of R. verniciflua extract on human aromatase (cytochrome P450 19, CYP19) activity was investigated to elucidate the mechanism for the effect of R. verniciflua extract on androgen hormone levels. Androstenedione was used as a substrate and incubated with R. verniciflua extract in cDNA-expressed CYP19 supersomes in the presence of NADPH, and estrone formation was measured using liquid chromatography–tandem mass spectrometry. R. verniciflua extract was assessed at concentrations of 10–1000 μg/mL. The resulting data showed that R. verniciflua extract inhibited CYP19-mediated estrone formation in a concentration-dependent manner with an IC₅₀ value of 136 μg/mL. Subsequently, polyphenolic compounds from R. verniciflua extract were tested to identify the ingredients responsible for the aromatase inhibitory effects by R. verniciflua extract. As a result, butin showed aromatase inhibitory effect in a concentration-dependent manner with an IC₅₀ value of 9.6 μM, whereas the inhibition by other compounds was negligible. These results suggest that R. verniciflua extract could modulate androgen hormone levels via the inhibition of CYP19 activity and butin is a major ingredient responsible for this activity.     

Terpenes of Podocarpus lambertius

Sitosterol and the following terpenic compounds have been isolated from the bark of Podocarpus lambertius: 3β-hydroxytotarol, 4β-carboxynortotarol, and macrophyllic and lambertic acids. The leaves yielded sitosterol, stigmastan-3β,5α-diol-6-one, isopimaric acid, phyllocladene, isophyllocladene, 8,9-abieten-15-ol and 17-isophyllocladenol.     

Diterpenes of Podocarpus ferrugineus bark

The following oxygenated diterpenes have been isolated from the bark of Podocarpus ferrugineus D. Don: isopimarol, isopimaric acid, sandaracopimaric acid, ferruginol, sugiol, sugiyl methyl ether, xanthoperol, royleanone, 6-dehydroroyleanone, cryptojaponol, 5β-hydroxy-6-oxasugiyl methyl ether, 2-ketoferruginol and 2β-acetoxysugiyl methyl ether.     

Expression analysis of Fgf8a & Fgf8b in early stage of P19 cells during neural differentiation

Fgf8 is a member of the fibroblast growth factor (FGF) family that plays an important role in early neural development. Cellular aggregation and retinoic acid (RA) are needed for mouse embryonic carcinoma (EC) P19 cell neural differentiation. We have examined the Fgf8 gene in P19 cells during neural differentiation and identified 2 alternatively spliced Fgf8 isoforms, Fgf8a and Fgf8b, among the 8 known splicing isoforms in mammals. The expression of Fgf8a and Fgf8b mRNAs transiently and rapidly increased in the early stage of P19 cells during RA-induced neural differentiation, followed by a decline in expression. The relative amount of Fgf8b was clearly higher than that of Fgf8a at different time-points measured within 24 h after RA treatment. Increased Fgf8b mRNA expression was cellular-aggregation dependent. The results demonstrated that cellular-aggregation-induced Fgf8b, but not Fgf8a, may play a pivotal role in early neural differentiation of P19 cells.     

Ethnobotany,phytochemistry and pharmacology of Podocarpus sensu latissimo (s.l.)

The genus Podocarpus sensu latissimo (s.l.) was initially subdivided into eight sections. However, based on new information from different morphological and anatomical studies, these sections were recognised as new genera. This change in nomenclature sometimes is problematic when consulting ethnobotanical data especially when selecting plants for pharmacological screening, thus there is a need to clear any ambiguity with the nomenclature. Species of Podocarpus s.l. are important timber trees in their native areas. They have been used by many communities in traditional medicine and as a source of income. Podocarpus s.l. is used in the treatment of fevers, asthma, coughs, cholera, distemper, chest complaints and venereal diseases. Other uses include timber, food, wax, tannin and as ornamental trees. Although extensive research has been carried out on species of Podocarpus s.l over the last decade, relatively little is known about the African species compared to those of New Zealand, Australia, China and Japan. Phytochemical studies have led to the isolation and elucidation of various terpenoids and nor- and bis-norditerpenoid dilactones. Biflavonoids of the amentoflavone and hinokiflavone types have also been isolated. Nor- and bis-norditerpenes are said to be taxonomic markers for this genus. Recent in vitro and in vivo studies have shown antitumor, antimicrobial, anti-inflammatory, antioxidant, larvicidal, plant and insect growth regulation activities. Various studies have yielded important natural bioactive products and two of them are worth mentioning. Taxol, a significant anticancer agent has been isolated from Podocarpus gracilior and totarol, a diterpenoid isolated from various species and now commercially produced as a potent antibacterial and antioxidant agent. Findings from this review supports the use of an ethnobotanical and chemotaxonomical approach in selecting plants for pharmacological screening since most of the species in the different morphological groups have similar uses. Also the isolated compounds have chemotaxonomic value amongst the groups. Some of the biological activities identified from extracts and compounds isolated from Podocarpus s.l. support the rationale behind the medicinal uses of these species.     

Reproductive biology and population structures of Podocarpus falcatus and P. latifolius in southern Gape forests

GELDENHUYS, C. J., 1993. Reproductive biology and population structures of Podocarpus falcatus and P. latifolius in southern Cape forests This study concerns morphological differences of the fruit types of two Podocarpus species in relation to their different population recruitment rates. First, sampling data from the mixed evergreen forests of Gouna and Groenkop in the southern Cape, South Africa, were used to describe the population structures of the two species. Podocarpus falcatus is widely scattered at low density and has a low recruitment rate. Podocarpus latifolius is widespread and common at high density and has a high recruitment rate. Second, the morphology of their fruits and seeds was studied in relation to seed dispersal, predation and germination. The species represent the two basic ‘fruit’ types of the genus. Podocarpus falcatus produces a heavy fruit, but invests mostly in dispersal (with a yellow fleshy pulp or epimatium enclosing the seed) and protective tissue (stony shell or sclerotesta) and very little into endosperm food reserves for the embryo. Podocarpus latifolius produces a light fruit which is composed mainly of dispersal tissue (blackish-purple fleshy receptacle) with protective tissue (thin leathery epimatium without woody sclerotesta) and food reserves for the embryo. The structure of the P. falcatus fruit is related to adaptation for protection during seed dispersal by bats. The stony sclerotesta delays germination for about one year and thereby causes the exposure of the seed to high post-dispersal predation by rodents and bushpig. Seedling recruitment is low. In contrast birds and baboons eat the receptacle of the P. latifolius fruit and discard the seed undamaged. Less protective tissue is required. Seeds germinate within two to four months and recruitment is high. The structural differences of the two fruit types also have predictive value for the relative success of the different sections of the genus. Section Afrocarpus (to which P. falcatus belongs) and related sections have relatively restricted geographic distributions. Section Eupodocarpus (to which P. latifolius belongs) and related sections have wide distributions.     

Pseudomonas aeruginosa cytochrome P450 CYP168A1 is a fatty acid hydroxylase that metabolizes arachidonic acid to the vasodilator 19-HETE

Pseudomonas aeruginosa is a Gram-negative opportunistic human pathogen that is highly prevalent in individuals with cystic fibrosis (CF). A major problem in treating CF patients infected with P. aeruginosa is the development of antibiotic resistance. Therefore, the identification of novel P. aeruginosa antibiotic drug targets is of the utmost urgency. The genome of P. aeruginosa contains four putative cytochrome P450 enzymes (CYPs) of unknown function that have never before been characterized. Analogous to some of the CYPs from Mycobacterium tuberculosis, these P. aeruginosa CYPs may be important for growth and colonization of CF patients’ lungs. In this study, we cloned, expressed, and characterized CYP168A1 from P. aeruginosa and identified it as a subterminal fatty acid hydroxylase. Spectral binding data and computational modeling of substrates and inhibitors suggest that CYP168A1 has a large, expansive active site and preferentially binds long chain fatty acids and large hydrophobic inhibitors. Furthermore, metabolic experiments confirm that the enzyme is capable of hydroxylating arachidonic acid, an important inflammatory signaling molecule present in abundance in the CF lung, to 19-hydroxyeicosatetraenoic acid (19-HETE; K_m = 41 μM, V_max = 220 pmol/min/nmol P450), a potent vasodilator, which may play a role in the pathogen’s ability to colonize the lung. Additionally, we found that the in vitro metabolism of arachidonic acid is subject to substrate inhibition and is also inhibited by the presence of the antifungal agent ketoconazole. This study identifies a new metabolic pathway in this important human pathogen that may be of utility in treating P. aeruginosa infections.     

The course of resin canals in the shoots of conifers

The course of resin canals in stem cortex and the continuity between resin canals in leaves and those in stem cortex were investigated. The present paper is the first of three parts of the investigation. In this paper, fundamental features of resin canals and actual resin canal patterns in the Taxaceae, Cephalotaxaceae and Podocarpaceae are reported. From the observation of serial transections of shoots, composite diagrams and three-dimensional models of resin canal patterns are drawn. Central canals, if present, run vertically in stem cortex and sometimes divide, end blindly or unite each other. The distance between two adjacent central canals fluctuates rhythmically in connection with the vascular supply from the stem to leaves. The resin canal patterns of the families are classified into four types. Those ofTaxus, Nothotaxus and three species ofDacrydium belong to the Taxus type, those ofTorreya andCephalotaxus to the Torreya type, those ofDacrydium elatum, Podocarpus alpinus, P. elatus, P. elongatus andP. neriifolius to the Dacrydium type, those ofP. macrophyllus, P. nagi andP. koordersii to the Podocarpus type.     

Biflavones from the genus Podocarpus

A new biflavonoid, podocarpusflavanone, has been isolated from Podocarpus taxifolia and identified by chemical and spectral data as I-4′,I-5,II-5-trihydroxy-II-4′,I-7,II-7-trimethoxy-I-2,3-dihydro-[I-3′,II-8]biflavone along with other biflavonoids. The distribution of biflavonyl pigments in eight Podocarpus species is outlined.     

Anhydrobartogenic acid and 19-epibartogenic acid,two triterpenes from Barringtonia speciosa

Two new triterpene dicarboxylic acids, isolated from the fruits of Barringtonia speciosa, have been identified as anhydrobartogenic acid and 19-epibartogenic acid by spectral and chemical evidence.     

Malaria,COVID-19 and angiotensin-converting enzyme 2: what does the available population data say?

The etiopathogenesis of COVID-19 and its differential geographic spread suggest some populations are apparently ‘less affected’ through many host-related factors that involve angiotensin-converting enzyme 2 (ACE2) protein, which is also the entry receptor for SARS-CoV-2. The role of ACE2 has been well studied in COVID-19 but not in the context of malaria and COVID-19. We have previously suggested how malaria might intersect with COVID-19 through ACE2 mutation and here we evaluate the currently available data that could provide a link between the two diseases. Based on the existing global and Indian data on malaria, COVID-19 and the suggested ACE2 mutation, the association could not be examined robustly, neither accepting nor refuting the suggested hypothesis. We strongly recommend targeted evaluation of this hypothesis through carefully designed robust molecular epidemiological studies.     

Four new diterpenoid alkaloids from Delphinium elatum

Diterpenoid alkaloids exhibit remarkable chemical properties and biological activities. Such compounds are frequently found in plants of the genera Aconitum, Delphinium, and Garrya. Several diterpenoid alkaloid components from Delphinium elatum cv. Pacific Giant and their derivatives exhibited cytotoxic activity against lung, prostate, nasopharyngeal, and vincristine-resistant nasopharyngeal cancer cell lines. Phytochemical investigations on the seeds of D. elatum cv. Pacific Giant led to the isolation of four new C₁₉-diterpenoid alkaloids, melpheline (1), 19-oxoisodelpheline (2), N-deethyl-19-oxoisodelpheline (3), and N-deethyl-19-oxodelpheline (4). The isolated alkaloids were elucidated by extensive spectroscopic methods including NMR (1D and 2D), IR, and MS (HRMS).