Isolation and Characterization of Phenylpropanoid and Lignan Compounds from Peperomia pellucida [L.] Kunth with Estrogenic Activities

Abstract

Extracts of Peperomia pellucida [L.] Kunth have previously been demonstrated to have in vivo estrogenic-like effects, thereby functioning as an anti-osteoporotic agent. However, the compounds responsible for these effects have not yet been determined. Therefore, the aim of this study is to isolate and elucidate potential compounds with estrogenic activity. The structures of the isolated compounds were identified using 1D 1H and 13C-NMR and confirmed by 2D FT-NMR. The estrogenic activity was evaluated using the E-SCREEN assay, and a molecular docking study was performed to predict the binding affinity of the isolated compounds to estrogen receptors. In this experiment, we successfully isolated three phenylpropanoids and two lignan derivatives, namely, 6-allyl-5-methoxy-1,3-benzodioxol-4-ol (1), pachypostaudin B (2), pellucidin A (3), dillapiole (4), and apiol (5). Among these compounds, the isolation of 1 and 2 from P. pellucida is reported for the first time in this study. Activity assays clearly showed that the ethyl acetate extract and its fractions, subfractions, and isolated compounds exerted estrogenic activity. Methanol fraction of the ethyl acetate extract produced the highest estrogenic activity, while 1 and 2 had partial agonist activity. Some compounds (derivates of dillapiole and pellucidin A) also had, in addition, anti-estrogenic activity. In the docking study, the estrogenic activities of 1–5 appeared to be mediated by a classical ligand-dependent mechanism as suggested by the binding interaction between the compounds and estrogen receptors; binding occurred on Arg 394 and His 524 of the alpha receptor and Arg 346 and His 475 of the beta receptor. In summary, we reveal that P. pellucida is a promising anti-osteoporotic agent due to its estrogenic activity, and the compounds responsible for this activity were found to be lignan and phenylpropanoid derivatives. The presence of other compounds in either the extract or fraction may contribute to a synergistic effect, as suggested by the higher estrogenic activity of the methanol fraction. Hence, we suggest further research on the osteoporotic activity and safety of the identified compounds, especially regarding their effects on estrogen-responsive organs.

Biosynthesis of Pellucidin A in Peperomia pellucida (L.) HBK

“…Nevertheless, the in vivo irradiation of plants under UV 365 light led to an almost 200% increase in the content of pellucidin A ( Supplementary Figure 2 ). Additional compounds that could be produced from dimerization of styrenes are pachypostaudin B, which has already been isolated from the extracts of P. pellucida ( Kartika et al, 2020 ). However, pachypostaudins A and B are found as racemates in the extracts of P. staudtii bark, and were also obtained by thermal dimerization of 2,4,5-trimethoxystyrene ( Ngadjui et al, 1989 ).…”

Biochemometry-Based Discovery of Phenylpropanoids from Azadirachta indica Fruits as Inhibitors of In Vitro Osteoclast Formation

“…They are hydroxycinnamyl alcohol monomers that form building blocks of many important bioactive phytochemicals. Although there are many reports on the anti-osteoporotic activity of phenylpropanoids [ 31 ], investigations on the molecular level are limited [ 32 , 33 , 34 ]. Some phenylpropanoids possess the capacity to positively modulate the metabolism of OB.…”

Peperomia pellucida extracts stimulates bone healing in alveolar socket following tooth extraction

“…1 Its effect on bone is promoted by its oestrogenic effect, its ability to induce calcium homeostasis, anabolic effects on osteoblasts, inhibition of osteoclastogenesis, antioxidant effects, and bone-related nutritional content. 2 , 3 , 4 , 5 , 6 , 7 , 8 Additionally, the analgesic, anti-inflammatory and antibacterial effects of this plant may be beneficial in wound treatment, including healing tooth sockets at post-extraction. The anti-inflammatory, antihemorrhagic, and wound healing properties of this plant have been mentioned in Ayurveda records.…”