Uncovering the inhibitory potentials of Phyllanthus nivosus leaf and its bioactive compounds against Plasmodium lactate dehydrogenase for malaria therapy.

Malaria control efforts have been hampered due to the emergence of resistant malaria parasite strains and the coinciding events of Covid-19. The quest for more effective and safe treatment alternatives is driving a slew of new studies that must be accelerated if malaria can be overcome. Due to its reported antimalarial activity, we studied the effects of extract and fractions of Phyllanthus nivosus leaf on Plasmodium lactate dehydrogenase (pLDH) activity using an in vitro assay. This was followed by an anti-plasmodial study using Plasmodium berghei-infected mice and an in silico identification of the plant's phytochemicals with possible pLDH-inhibitory activity. The activity of pLDH was significantly reduced in the presence of ethanol extract and various solvent fractions of Phyllanthus nivosus leaf, with the ethyl acetate fraction having the best inhibitory activity, which was comparable to that of the standard drug (chloroquine). The ethyl acetate fraction at 100 and 200 mg/Kg also suppressed the parasitaemia of Plasmodium berghei-infected mice by 76 and 80% respectively. Among the 53 compounds docked against pLDH, (-)-alpha-Cadinol, (+)-alpha-phellandrene, and spathulenol, all terpenes from the ethyl acetate fraction of P. nivosus leaf extract, demonstrated docking scores comparable to that of chloroquine. The three chemicals, like chloroquine, displayed important molecular interactions with the amino acid residues of the enzyme's NADH-binding site. According to the in silico ADMET study, the three terpenes have suitable drug-like abilities, pharmacokinetic features, and safety profiles. Hence, they could be considered for further development as antimalarial drugs.Communicated by Ramaswamy H. Sarma.

Alpha-Phellandrene and Alpha-Phellandrene-Rich Essential Oils: A Systematic Review of Biological Activities, Pharmaceutical and Food Applications.

Alpha-phellandrene is a very common cyclic monoterpene found in several EOs, which shows extensive biological activities. Therefore, the main focus of the present systematic review was to provide a comprehensive and critical analysis of the state of the art regarding its biological activities and pharmaceutical and food applications. In addition, the study identified essential oils rich in alpha-phellandrene and summarized their main biological activities as a preliminary screening to encourage subsequent studies on their single components. With this review, we selected and critically analyzed 99 papers, using the following bibliographic databases: PubMed, SciELO, Wiley and WOS, on 8 July 2022. Data were independently extracted by four authors of this work, selecting those studies which reported the keyword "alpha-phellandrene" in the title and/or the abstract, and avoiding those in which there was not a clear correlation between the molecule and its biological activities and/or a specific concentration from its source. Duplication data were removed in the final article. Many essential oils have significant amounts of alpha-phellandrene, and the species Anethum graveolens and Foeniculum vulgare are frequently cited. Some studies on the above-mentioned species show high alpha-phellandrene amounts up to 82.1%. There were 12 studies on alpha-phellandrene as a pure molecule showed promising biological functions, including antitumoral, antinociceptive, larvicidal and insecticidal activities. There were 87 research works on EOs rich in alpha-phellandrene, which were summarized with a focus on additional data concerning potential biological activities. We believe this data is a useful starting point to start new research on the pure molecule, and, in particular, to distinguish between the synergistic effects of the different components of the OEs and those due to alpha-phellandrene itself. Toxicological data are still lacking, requiring further investigation on the threshold values to distinguish the boundary between beneficial and toxic effects, i.e., mutagenic, carcinogenic and allergenic. All these findings offer inspiration for potential applications of alpha-phellandrene as a new biopesticide, antimicrobial and antitumoral agent. In particular, we believe our work is of interest as a starting point for further studies on the food application of alpha-phellandrene.

Ethosomal Gel Formulation of Alpha Phellandrene for the Transdermal Delivery in Gout.

Purpose: Purpose was to improve the skin compatibility and permeability of alpha phellandrene through an ethosomal gel formulation for the treatment of gout; as the oral use of the drug is reported to cause gastrointestinal disturbances and toxicities. Methods: Alpha phellandrene loaded ethosomal formulation (APES) was prepared by cold method for the treatment of gout. APES were loaded into carbopol gel (APEG) by dispersion method. Physico-chemical characterizations of the APES were done by dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FTIR) etc. In vitro release, permeation, haemo-compatibility and anti-inflammatory studies were conducted. Results: APES showed a particle size of 364.83 ± 45.84 nm. The entrapment efficiency of the optimized formulation is found as 95.06 ± 2.51%. Hemolysis data indicated that APES does not cause any significant hemolysis. In vitro drug release studies were carried out using dialysis membrane technique and the amount of drug released from APES & APEG is found to be 95% and 94.21% respectively after 5 and6 hours. Kinetic data analysis revealed that APES & APEG follows first order and zero order release kinetics, respectively. The anti-inflammatory activity studies of the formulation are done by estimating its inhibitory effects on cyclooxygenase II (COX) II, lipoxygenase-5 (LOX-5), Myeloperoxidase (MPO), Inducible nitric oxide synthase (INOS) & cellular nitrite level using RAW 264.7 cells. The significant inhibition in the activities of the enzymes implies the anti-inflammatory activity of the formulations. Skin permeation study was carried out using porcine skin and revealed that the permeation of alpha phellandrene is increased from APES & APEG when compared with alpha-phellandrene solution (APS). Skin deposition study of APS, APES & APEG revealed better drug deposition from APEG (48.799 ± 1.547µg/cm2 ) after 24 hours when compared with APS & APES. Conclusion: Overall results indicate that the ethosomal formulation of alpha phellandrene through transdermal route is an effective alternative for oral use of the drug.

A review of the relaxant effect of various medicinal plants on tracheal smooth muscle, their possible mechanism(s) and potency.

ETHNOPHARMACOLOGICAL RELEVANCE: The therapeutic effects of the medicinal plants described in the current review on obstructive pulmonary diseases have found mention in ancient Iranian medical texts and in traditional folk medicine. These effects are attributed to their bronchodilatory activity, which relaxes the smooth muscles of the airway. Therefore, in the present review, the relaxant effects of various extracts, fractions and constituents of medicinal plants on tracheal smooth muscle are reviewed in light of their therapeutic effects on obstructive pulmonary diseases. MATERIALS AND METHODS: The online literature was searched using Medline, PubMed, ScienceDirect, Scopus, Google Scholar, Web of Science and SID (for articles written in Persian). Moreover, local books on ethnopharmacology from 1918 to 2014 were searched with keywords such as tracheal smooth muscle, airway smooth muscle, relaxant effect, bronchodilatory effect and related mechanisms to identify studies on the relaxant effects of medicinal plants on tracheal smooth muscle and the possible mechanism(s) of these effects. RESULTS: All studied plants showed significant relaxant effects on tracheal smooth muscle, which were similar or superior to the effect of theophylline at the used concentrations. According to the results, most of these plants also showed an inhibitory effect on muscarinic and histamine (H1) receptors, whereas some plants showed more pronounced stimulatory effects on the beta-adrenergic receptor. Some of the studied plants also showed inhibitory effects on calcium and potassium channels. CONCLUSION: The present article reviewed the relaxant effects of several medicinal plants on tracheal smooth muscle, which were comparable or superior to the effect of theophylline at the studied concentration. The possible mechanisms of the relaxant effects of the studied medicinal plants and a comparison of these effects were also reviewed. This review presents the fractions and constituents of plants with potent relaxant effects on tracheal smooth muscle, which can be used to treat obstructive pulmonary disease.

Composition of the essential oil from leaves of Smallanthus quichensis (Asteraceae) from Costa Rica / Composición química del aceite esencial de las hojas de Smallanthus quichensis (Asteraceae) de Costa Rica

Smallanthus is a genus of flowering plants in the Asteraceae family, which has about 24 species, ranging mostly from southern Mexico and Central America to the Andes in South America. The aim of the present study was to identify the chemical composition of leaf essential oil of S. quichensis, growing wild in Costa Rica. The extraction of the oils was carried out by the hydrodistillation method, using a modified Clevenger type apparatus. The chemical composition of the oils was analyzed by capillary GC-FID and GC-MS using the retention indices on DB-5 type capillary column. A total of 100 compounds were identified, accounting for about 90 percent of the total amount of the oils. Smallanthus quichensis leaf produced a monoterpenoid-rich oil, whose composition was dominated by αlfa-pinene (64.5 percent) and 1,8-cineole (9.7 percent) or, in a different sample, by αlfa-pinene (35.5 percent) with moderate amounts of p-cymene (11.5 percent), beta-phellandrene (9.2 percent), alfa-phellandrene (9.0 percent) and limonene (5.8 percent). This is the first report of the chemical composition of the essential oil obtained from this plant species.

Smallanthus es un género de plantas perteneciente a la familia Asteraceae que contiene aproximadamente 24 especies, la mayoría ubicadas desde el sur de México, América Central y hasta la cordillera de los Andes en América del Sur. El objetivo del presente estudio fue el de identificar la composición química del aceite esencial de las hojas de S. quichensis. La extracción se realizó mediante el método de hidrodestilación, empleando un instrumento de tipo Clevenger. Se analizó la composición de los aceites mediante CG-FID y CG-EM, utilizando índices de retención obtenidos en una columna capilar tipo DB-5. Se identificaron 100 compuestos, correspondientes a un 90 por ciento de los constituyentes totales. Los aceites están constituidos principalmente por monoterpenoides (ca. 85 por ciento). Los componentes mayoritarios se identificaron como alfa-pineno (64.5 por ciento), acompañado por 1,8-cineol (9.7 por ciento) o, en otra muestra distinta, αlfa-pineno (35.5 por ciento) junto a cantidades moderadas de p-cimeno (11.5 por ciento), beta-felandreno (9.2 por ciento), alfa-felandreno (9.0 por ciento) y limoneno (5.8 por ciento). Este es el primer informe acerca de la composición química de aceites esenciales obtenidos de S. quichensis.