Jasmonates promote enhanced production of bioactive caffeoylquinic acid derivative in Eclipta prostrata (L.) L. hairy roots.

Eclipta prostrata (L.) L. is widely used in traditional medicine for treatment of hepatitis, poisoning from snake bites and viral infections. Pharmacological studies confirmed its antioxidant, anti-inflammatory and anticancer activities. The efficacy of E. prostrata (L.) L. extracts has been correlated to phenylpropanoids such as flavonoids, coumestans and caffeoylquinic acid derivatives. In this work, the production of wedelolactone, demethylwedelolactone and 3,5-di-O-caffeoylquinic acid (3,5-diCQA) in hairy root cultures of E. prostrata (L.) L. C19 clone was increased after addition of eliciting agents jasmonic acid (JA) or methyl jasmonate (MeJA) at multiple concentrations. Cultures elicited with 100 µM of JA saw a 5.2 fold increase in wedelolactone (from 0.72 to 3.72 mg/g d.w.), a 1.6 fold increase in demethylwedelolactone (from 5.54 to 9.04 mg/g d.w.) and a 2.47 fold increase in 3,5-diCQA (from 18.08 to 44.71 mg/g d.w.). Obtained data validate the potential of E. prostrata (L.) L. hairy root cultures as a production system of wedelolactone, demethylwedelolactone and especially 3,5-diCQA, which has recently been reported to possess activity against coronavirus disease (Covid-19) by in silico computational studies. Supplementary Information: The online version contains supplementary material available at 10.1007/s11240-021-02201-4.

Genetic diversity among genotypes of Uncaria guianensis (Aubl.) J.F. Gmel. maintained in an in vitro germplasm bank.

Phytotherapeutic preparations from Uncaria guianensis (Aubl.) J.F. Gmel. (Rubiaceae) are marketed worldwide and are mainly used for their anti-inflammatory activity. The species has not yet been domesticated and is threatened by deforestation and overexploitation. It is, therefore, important to preserve and manage this genetic resource in germplasm banks, so that the extractive provision of plant material can be replaced by cultivated production. The aim of this study was to evaluate the genetic diversity among 20 genotypes maintained under in vitro conditions using 9 primers start codon targeted (SCoT) polymorphism, and to determine the concentrations of the pentacyclic oxindole alkaloids (POAs); mitraphylline and isomitraphylline in methanolic extracts by high-performance liquid chromatography (HPLC). Plantlets were cultivated on woody plant medium supplemented with 20 g.L-1 sucrose and 4.4 µM benzylaminopurine and incubated under a 16 h photoperiod for 45 days. SCoT analysis separated the genotypes into four divergent clusters and confirmed significant genetic diversity with up to 70% dissimilarity. Moreover, HPLC revealed considerable chemical variability and allowed the separation of the tested genotypes into high, medium and low producers of mitraphylline/isomitraphylline. Genotypes with the highest concentrations of POAs originated from the state of Acre and Amapá, while those with the lowest levels were from the state of Pará. The results demonstrate that the genetic diversity within the in vitro germplasm bank is sufficient to support breeding studies, selection of elite genotypes and the large-scale multiplication of plants that could serve as feedstock for the industrial-scale production of phytomedicines. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13205-021-03016-y.

Geranylation of benzoic acid derivatives by enzymatic extracts from Piper crassinervium (Piperaceae).

The ability to carry out geranylations on aromatic substrates using enzymatic extracts from the leaves of Piper crassinervium (Piperaceae) was evaluated. A literature analysis pointed out its importance as a source of prenylated bioactive molecules. The screening performed on aromatic acceptors (benzoic acids, phenols and phenylpropanoids) including geranyl diphosphate as prenyl donor, showed the biotransformation of the 3,4-dihydroxybenzoic acid by the crude extract, and the p-hydroxybenzoic acid by both the microsomal fraction and the crude extract, after treating leaves with glucose. The analysis of the products allowed the identification of C- and O-geranylated derivatives, and the protease (subtilisin and pepsin) inhibition performed on the O-geranylated compounds showed weak inhibition. Electrophoretic profiles indicated the presence of bands/spots among 56-58 kDa and pI 6-7, which are compatible with prenyltransferases. These findings show that P. crassinervium could be considered as a source of extracts with geranyltransferase activity to perform biotransformations on aromatic substrates.

In vitro activity of compounds isolated from Piper crassinervium against Trypanosoma cruzi.

This study describes the antichagasic potential of five compounds isolated from leaves of Piper crassinervium (Piperaceae). Two prenylated benzoic acid derivatives, one prenylated hydroquinone and two flavanones, were evaluated. The in vitro trypanocidal activity was determined against epimastigote forms of Trypanosoma cruzi (Y strain), the etiologic agent of Chagas disease. The most active compound was the prenylated hydroquinone [1,4-dihydroxy-2-(3(0),7(0)-dimethyl-1(0)-oxo-2(0)-E,6(0)-octadienyl)benzene] with an IC(50) value of 6.10 microg mL(-1), which was in the same order of activity if compared with the positive control benznidazole (IC(50) = 1.60 microg mL(-1)). This is the first report of trypanocidal activity for prenylated hydroquinone and benzoic acid derivatives.

Natural chromenes and chromene derivatives as potential anti-trypanosomal agents.

The aim of the study was to investigate the anti-trypanocidal activities of natural chromene and chromene derivatives. Five chromenes were isolated from Piper gaudichaudianum and P. aduncum, and a further seven derivatives were prepared using standard reduction, methylation and acetylation procedures. These compounds were assayed in vitro against epimastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. The results showed that the most of the compounds, especially those possessing electron-donating groups as substituents on the aromatic ring, showed potent trypanocidal activity. The most active compound, [(2S)-methyl-2-methyl-8-(3''-methylbut-2''-enyl)-2-(4'-methylpent-3'-enyl)-2H-chromene-6-carboxylate], was almost four times more potent than benznidazole (the positive control) and showed an IC50 of 2.82 microM. The results reveal that chromenes exhibit significant anti-trypanocidal activities and indicate that this class of natural product should be considered further in the development of new and more potent drugs for use in the treatment of Chagas disease.