Chemical profile and in vivo toxicity evaluation of unripe Citrus aurantifolia essential oil

Citrus aurantifolia (Christm.) Swingle (syn. C. MEDICA var. ACIDA Brandis) (family: Rutaceae) essential oil is one of the cheapest oils found in local markets. Although, it is generally accepted as non-toxic to vital organs and cells, majority of people are cynical about it usage. Herein, the present study reports the chemical composition and in vivo oral toxicity study of unripe C. aurantifolia essential oil found in Ghana. The toxicity of C. aurantifolia essential oil extract was investigated via oral administration using two methods: The acute toxicity single dose study (SDS) and the repeated dose method. The oil exhibited no acute toxicity but in the sub-chronic studies, the effects was dose and time-dependent. Chemical profile investigation of the oil showed 9 constituent of phytochemicals (Germacrene isomers (61.2%), Pineen (14%), Linalool dimmer (2.9%), Bornane (11%), Citral (2.9%), Anethole (1.5%), Anisole (1.1%), Safrole (0.3%) and Demitol (0.6%)). Histopathological studies revealed conditions such as necrosis, edema and inflammatory reaction in the liver, spleen and kidneys. Marginal upsurge of biochemical parameters above normal and elevated levels of lymphocytes (35.20–46.40 g/dL) demonstrated mild toxicity among the 100 mg/kg and 500 mg/kg dose groups at the sub-chronic stage. Low levels of hemoglobin (13.60 to 12.70 g/dL), MCV (34.20–24.0 fL), MCH (40.20–36.40 g/dL) along with high levels of liver enzymes confirmed the mild toxicity of the oil at sub-chronic stage. These results demonstrate that, despite consideration of lime essential oil as safe, it can have mild hematotoxic, nephrotoxic and hepatotoxic effects

Regiospecific Synthesis of 2‑Halo-3-(2′-glucalyl)benzo[<i>b</i>]thiophenes

A regiospecific synthetic strategy for the synthesis of 2-chloro-3-substituted benzo­[<i>b</i>]­thiophenes is developed via a dichlorocarbene insertion and sigmatropic rearrangement of an in situ generated ylide. The current protocol provides a reversed regiochemistry to the commonly employed electrophilic cyclization reaction for the synthesis of benzo­[<i>b</i>]­thiophenes and access to their hitherto under-represented chlorinated derivatives

Toxicity and therapeutic applications of citrus essential oils (CEOs): a review

ABSTRACTCitrus essential oil (CEO) is obtained from the fruit of Genus Citrus, a flowering plant shrub in the family of the Rutaceae (Eremocitrus or Microcitrus) and extensively used in food, chemical industry, and traditional medicinal treatment owing to its pleasant aroma, antioxidant, and antiseptic properties. This review presents a botanical description, distribution, traditional uses, chemical composition, bioactive components, and the therapeutic uses as well as toxicological effects of the CEO. The objective was achieved via a comprehensive literature search of electronic databases such as Science Direct, PubMed, Web of Science, Wiley, ACS, Springer, Taylor and Francis, Google Scholar, SCOPUS, conference proceedings, thesis, and books until 2022 for publications. Citrus essential oils and their constituents are extracted and isolated either from the fruit peels, seeds, leaves, or flowers of the citrus plants. A comparative study of the sources of CEO confirmed its origin, ethnopharmacological and therapeutic uses. Over 2000 secondary metabolites have been isolated, with the main active constituents: being terpenes, monoterpenes, sesquiterpenes, and diterpenes. A comprehensive literature review revealed vast therapeutic benefits of CEO. Incomplete data report on in vitro and in vivo trials especially, on dosage, positive and negative control groups, intervention time, toxicity studies, phytochemical profiling, and clinical trials seem to be a knowledge gap

Alkaloidal Extracts from Avicennia africana P. Beauv. (Avicenniaceae) Leaf: An Antiplasmodial, Antioxidant, and Erythrocyte Viable

Background. The emergence of drug-resistant parasites impedes disease management and eradication efforts. Hence, a reinvigorated attempt to search for potent lead compounds in the mangroves is imperative. Aim. This study evaluates in vitro antiplasmodial activity, antioxidant properties, and cytotoxicity of A. africana leaf alkaloidal extracts. Methods. The A. africana leaves were macerated with 70% ethanol to obtain a total crude extract. Dichloromethane and chloroform-isopropanol (3 : 1, v/v) were used to extract the crude alkaloids and quaternary alkaloids from the total crude. The antiplasmodial activities of the alkaloidal extracts were performed against 3D7 P. falciparum chloroquine-sensitive clone via the SYBR Green I fluorescence assay with artesunate serving as the reference drug. The alkaloidal extracts were further evaluated for antioxidant properties via the total antioxidant capacity (TAC), the total glutathione concentration (GSH), the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay, and the ferric-reducing antioxidant power (FRAP) methods. The cytotoxic activity of the alkaloidal extracts was tested on erythrocytes using a 3-(4,5-dimethylthiazol-2-yl)-5-diphenyltetrazolium bromide-MTT assay with little modification. The phytocompounds in the alkaloidal extracts were identified via gas chromatography-mass spectrometry (GC-MS) techniques. Results. The total crude extract showed good antiplasmodial activity (IC50 = 11.890 µg/mL). The crude and quaternary alkaloidal extracts demonstrated promising antiplasmodial effects with IC50 values of 6.217 and 6.285 µg/mL, respectively. The total crude and alkaloidal extracts showed good antioxidant properties with negligible cytotoxicity on erythrocytes with good selectivity indices. The GC-MS spectral analysis of crude alkaloidal extracts gave indole and isoquinoline alkaloids and several other compounds. Dexrazoxane was found to be the main compound predicted, with an 86% peak area in the quaternary alkaloidal extract. Conclusion. The crude and quaternary alkaloidal extracts exhibited antiplasmodial activities and ability to inhibit oxidative stress with negligible toxicity on erythrocytes. This may be good characteristics to avoid oxidative stress related to Plasmodium infection in the treatment of malaria

Synthesis and Evaluation of Glycopolymeric Decorated Gold Nanoparticles Functionalized with Gold-Triphenyl Phosphine as Anti-Cancer Agents

In this study, statistical glyco-dithiocarbamate (DTC) copolymers were synthesized by reversible addition–fragmentation chain transfer polymerization (RAFT) and subsequently used to prepare glyconanoparticles and conjugated glyconanoparticles with the anticancer drug, gold­(I) triphenylphosphine. These glyconanoparticles and the corresponding conjugates were then tested for their in vitro cytotoxicity in both normal and cancer cell lines using Neutral Red assay. The glyconanoparticles and their Au­(I)­PPh₃ conjugates were all active against MCF7 and HepG2 cells, but galactose-functionalized glyconanoparticles {P­(GMA-EDAdtc­(AuPPh₃)-st-LAEMA)­AuNP} were found to be the most cytotoxic to HepG2 cells (IC₅₀ ∼ 4.13 ± 0.73 μg/mL). The p­(GMA-EDAdtc­(AuPPh₃)-st-LAEMA)­AuNP was found to be a 4-fold more potent antitumor agent in HepG2 cells, and the overexpressed asialoglycoprotein (ASGPR) receptors revealed to play an important role in the cytotoxicity, presumably by the enhanced uptake. In addition, the glyconanoparticles Au­(I) conjugates are found to be significantly more toxic as compared to the standard chemotherapeutic reagents such as cisplatin and cytarabine