UHPLC-HRMS/MS Chemical Fingerprinting of the Bioactive Partition from Cultivated Piper aduncum L.

Piper aduncum L. is widely distributed in tropical regions and the ethnobotanical uses of this species encompass medicinal applications for the treatment of respiratory, antimicrobial, and gynecological diseases. Chemical studies reveal a diverse array of secondary metabolites, including terpenes, flavonoids, and prenylated compounds. Extracts from P. aduncum have shown antibacterial, antifungal, and larvicidal activities. Our study explores the activity of extracts and partitions against Mycobacterium tuberculosis H37Rv, as well as the chemical diversity of the bioactive partition. This marks the first investigation of the bioactive partition of P. aduncum from agroecological cultivation. The ethyl acetate partition from the ethanolic leaf extract (PAEPL) was found to be the most active. PAEPL was subjected to column chromatography using Sephadex LH-20 and the obtained fractions were analyzed using UHPLC-HRMS/MS. The MS/MS data from the fractions were submitted to the online GNPS platform for the generation of the molecular network, which displayed 1714 nodes and 167 clusters. Compounds were identified via manual inspection and different libraries, allowing the annotation of 83 compounds, including flavonoids, benzoic acid derivatives, glycosides, free fatty acids, and glycerol-esterified fatty acids. This study provides the first chemical fingerprint of an antimycobacterial sample from P. aduncum cultivated in an agroecological system.

Toll-like receptors in inflammatory bowel disease: A review of the role of phytochemicals.

BACKGROUND: Inflammatory bowel disease (IBD) is a chronic inflammation within the gastrointestinal tract with a remarkable impact on patients' quality of life. Toll-like receptors (TLR), as a key contributor of immune system in inflammation, has a critical role in the pathogenesis of IBD and thus, can be a suitable target of therapeutic agents. Medicinal plants have long been considered as a source of bioactive agents for different diseases, including IBD. PURPOSE: This review discusses current state of the art on the role of plant-derived compounds for the management of IBD with a focus on TLRs. METHODS: Electronic database including PubMed, Web of Science, and Scopus were searched up to January 2023 and all studies in which anticolitis effects of a phytochemical was assessed via modulation of TLRs were considered. RESULTS: Different categories of phytochemicals, including flavonoids, lignans, alkaloids, terpenes, saccharides, and saponins have demonstrated modulatory effects on TLR in different animal and cell models of bowel inflammation. Flavonoids were the most studied phytochemicals amongst others. Also, TLR4 was the most important type of TLRs which were modulated by phytochemicals. Other mechanisms such as inhibition of pro-inflammatory cytokines, nuclear factor-κB pathway, nitric oxide synthesis pathway, cyclooxygenase-2, lipid peroxidation, as well as induction of endogenous antioxidant defense mechanisms were also reported for phytochemicals in various IBD models. CONCLUSION: Taken together, a growing body of pre-clinical evidence support the efficacy of herbal compounds for the treatment of IBD via modulation of TLRs. Future clinical studies are recommended to assess the safety and efficacy of these compounds in human.

Aurelianolides from Aureliana fasciculata var. fasciculata Trigger Apoptosis With Caspase Activation in Human Leukemia Cells.

BACKGROUND/AIM: Aurelianolide A and B were identified and isolated from Aureliana fasciculata var. fasciculata leaves. Withanolides are naturally occurring C-28 steroidal lactone triterpenoids with cytotoxic and anticancer properties, among other relevant pharmacological activities. Herein we have described, for the first time, the cytotoxic effects of aurelianolides on human cancer cells. MATERIALS AND METHODS: Aurelianolide A and B were tested on human leukemia cell lines: THP-1, MOLT-4, Jurkat, K562 and K562-Lucena 1. RESULTS: For aurelianolide A, MOLT-4 had the lower IC50 (1.17 µM) and for aurelianolide B, Jurkat was the most susceptible cell line (IC50 2.25 µM). On the other hand, the multidrug resistant (MDR) cell line K562-Lucena 1 showed higher IC50 for both aurelianolides. Using 293T, a non-tumor embryonic kidney cell line, we observed an excellent selectivity index for both aurelianolides, from 2.24 (aurelianolide B in K562-Lucena 1) to 45.5 (aurelianolide A in MOLT-4). Aurelianolide A and B activated caspase 3/7 with consequent induction of apoptosis on Jurkat and K562-Lucena 1 cell lines. We have not observed induction of necrosis. CONCLUSION: Aurelianolides A and B have important cytotoxic effects on human leukemia cell lines by the activation of the caspase pathway.

Apoptotic effect of ß-pinene on oral squamous cell carcinoma as one of the major compounds from essential oil of medicinal plant Piper rivinoides Kunth.

Oral squamous cell carcinoma (OSCC) is the most common type of head and neck malignancy. Research on essential oils (EOs) has shown important cytotoxic and anti-tumor properties, among others. Piperaceae species are rich in EOs and here we highlight Piper rivinoides Kunth. We investigated the crude EOs from P. rivinoides, their pure major constituents and an enriched fraction with the main EO compounds (EF) as cytotoxic and selective OSCC agents. EOs presented as main compounds (-)-α-pinene, (-)-ß-pinene and limonene. EOs showed an IC50 lower than all isolated compounds, except for (-)-ß-pinene in OSCC cells. The (-)-ß-pinene induced cell death with apoptotic characteristics. Commercial standards showed greater selectivity than EOs, and (-)-ß-pinene was the most selective among them. EF showed higher selectivity compared to crude EOs and carboplatin, turning it into a good candidate as an anticancer fraction. These results are important for the possible development of new treatments for OSCC.

Vasodilator activity of the essential oil from aerial parts of Pectis brevipedunculata and its main constituent citral in rat aorta.

The essential oil of Pectis brevipedunculata (EOPB), a Brazilian ornamental aromatic grass, is characterized by its high content of citral (81.9%: neral 32.7% and geranial 49.2%), limonene (4.7%) and α-pinene (3.4%). Vasodilation induced by EOPB and isolated citral was investigated in pre-contracted vascular smooth muscle, using thoracic aorta from Wistar Kyoto (WKY) rats which was prepared for isometric tension recording. EOPB promoted intense relaxation of endothelium-intact and denuded aortic rings with the concentration to induce 50% of the maximal relaxation (IC50) of 0.044% ± 0.006% and 0.093% ± 0.015% (p < 0.05), respectively. The IC50 values for citral in endothelium-intact and denuded rings were 0.024% ± 0.004% and 0.021% ± 0.004%, respectively (p > 0.05). In endothelium-intact aorta, EOPB-induced vasorelaxation was significantly reduced by L-NAME, a nitric oxide synthase inhibitor. The vasodilator activity of citral was increased in the KCl-contracted aorta and citral attenuated the contracture elicited by Ca2+ in depolarized aorta. EOPB and citral elicited vasorelaxation on thoracic aorta by affecting the NO/cyclic GMP pathway and the calcium influx through voltage-dependent L-type Ca2+ channels, respectively.

Antileishmanial activity of nerolidol-rich essential oil from Piper claussenianum

Leishmaniasis is one of the most neglected tropical diseases, representing a group of parasitic diseases worldwide spread, occurring in 88 tropical and subtropical countries. Approximately 350 million people live in areas of active transmission of leishmaniasis, with about 1-2 million estimated new cases occurring every year. More than 90 percent of the cutaneous cases appear in developing countries. Efforts to improve the therapeutic arsenal against leishmaniasis have led to the search for new and cheap range of drugs. In this study, the nerolidol-rich essential oil from Piper claussenianum (Miq.) C. DC., Piperaceae, was assayed on arginase activity of Leishmania amazonensis. The effect of this essential oil on arginase activity levels showed an enzyme inhibition of 62.2 percent. This result stimulates the scientific interest about the potential value of this plant species on neglected diseases as potential new natural product source of pharmacological interest for the treatment of leishmaniasis.