Marianna Vieira Sobral

Antitumor Activity of Monoterpenes Found in Essential Oils

Cancer is a complex genetic disease that is a major public health problem worldwide, accounting for about 7 million deaths each year. Many anticancer drugs currently used clinically have been isolated from plant species or are based on such substances. Accumulating data has revealed anticancer activity in plant-derived monoterpenes. In this review the antitumor activity of 37 monoterpenes found in essential oils is discussed. Chemical structures, experimental models, and mechanisms of action for bioactive substances are presented.

Medicinal Plants and Other Living Organisms with Antitumor Potential against Lung Cancer

Lung cancer is a disease with high morbidity and mortality rates. As a result, it is often associated with a significant amount of suffering and a general decrease in the quality of life. Herbal medicines are recognized as an attractive approach to lung cancer therapy with little side effects and are a major source of new drugs. The aim of this work was to review the medicinal plants and other living organisms with antitumor potential against lung cancer. The assays were conducted with animals and humans, and Lewis lung carcinoma was the most used experimental model. China, Japan, South Korea, and Ethiopia were the countries that most published studies of species with antitumor activity. Of the 38 plants evaluated, 27 demonstrated antitumor activity. In addition, six other living organisms were cited for antitumor activity against lung cancer. Mechanisms of action, combination with chemotherapeutic drugs, and new technologies to increase activity and reduce the toxicity of the treatment are discussed. This review was based on the NAPRALERT databank, Web of Science, and Chemical Abstracts. This work shows that natural products from plants continue to be a rich source of herbal medicines or biologically active compounds against cancer.

Activity of Alkaloids on Peptic Ulcer: What’s New?

Peptic ulcer is a common disease characterized by lesions that affect the mucosa of the esophagus, stomach and/or duodenum, and may extend into the muscular layer of the mucosa. Natural products have played an important role in the process of development and discovery of new drugs, due to their wide structural diversity and present, mostly specific and selective biological activities. Among natural products the alkaloids, biologically active secondary metabolites, that can be found in plants, animals or microorganisms stand out. The alkaloids are compounds consisting of a basic nitrogen atom that may or may not be part of a heterocyclic ring. This review will describe 15 alkaloids with antiulcer activity in animal models and in vitro studies.

Essential oil from fruit of Xylopia langsdorffiana: antitumour activity and toxicity

Abstract Context: The genus Xylopia L. (Annonaceae) includes aromatic plants that have both nutritional and medicinal uses. Essential oils of Xylopia species have antitumour effects. However, the efficacy of the essential oil from the fruit of Xylopia langsdorffiana St. Hil & Tul. (EOX) has not been examined. Objective: EOX was evaluated to determine its chemical composition, antitumour activity and toxicity. Materials and methods: EOX was obtained from fresh fruits of X. langsdorffiana subjected to hydrodistillation, and gas chromatography-mass spectrometry was used to characterize the chemical composition of EOX. The toxicity of EOX was evaluated using haemolysis, acute toxicity and micronucleus assays. The in vitro antitumour activity of EOX was investigated using the sulforhodamine B assay. The sarcoma 180 murine tumour model was used to evaluate the in vivo antitumour activity and toxicity of EOX (50 and 100 mg/kg) after 7 d of treatment. Results: The major components of EOX were α-pinene (34.57%) and limonene (31.75%). The HC50 (concentration producing 50% haemolysis) was 293.6 μg/ml. EOX showed greater selectivity for the leukaemia cell line K562, with total growth inhibition (TGI) (concentration producing TGI) of 1.8 μg/ml, and for multidrug-resistant ovarian tumour cell line NCI/ADR-RES (TGI of 45.4 μg/ml). The LD50 was approximately 351.09 mg/kg. At doses of 50 and 100 mg/kg, EOX inhibited the in vivo growth of sarcoma 180 by 38.67 and 54.32%, respectively. EOX displayed minor hepatic alterations characteristic of acute hepatitis and induced no genotoxicity. Conclusion: EOX showed in vitro and in vivo antitumour activity and low toxicity, which warrants further pharmacological studies.

Chemical composition, antitumor activity, and toxicity of essential oil from the leaves of Lippia microphylla.

Abstract The chemical composition, antitumor activity and toxicity of the essential oil from Lippia microphylla leaves (OEL) were investigated. The major constituents were thymol (46.5%), carvacrol (31.7%), p-cymene (9%), and γ-terpinene (2.9%). To evaluate the toxicity of OEL in non-tumor cells, the hemolytic assay with Swiss mice erythrocytes was performed. The concentration producing 50% hemolysis (HC50) was 300 μg/mL. Sarcoma 180 tumor growth was inhibited in vivo 38% at 50 mg/kg, and 60% at 100 mg/kg, whereas 5-FU at 50 mg/kg caused 86% inhibition. OEL displays moderate gastrointestinal and hematological toxicity along with causing some alteration in liver function and morphology. However, the changes were considered reversible and negligible in comparison to the effects of several anticancer drugs. In summary, OEL displays in vivo antitumor activity and a moderate toxicity, which suggests further pharmacological study.

Th1-Biased Immunomodulation and In Vivo Antitumor Effect of a Novel Piperine Analogue

Natural products have an important role as prototypes in the synthesis of new anticancer drugs. Piperine is an alkaloid amide with antitumor activity and significant toxicity. Then, the N-(p-nitrophenyl)acetamide piperinoate (HE-02) was synthesized, and tested for toxicological and antitumor effects. The toxicity was evaluated in vitro (on RAW 264.7 cells and mice erythrocytes) and in vivo (acute toxicity in mice). The Ehrlich ascites carcinoma model was used to evaluate the antitumor activity of HE-02 (6.25, 12.5 or 25 mg/kg, intraperitoneally, i.p.), as well as toxicity. HE-02 induced only 5.01% of hemolysis, and reduced the viability of RAW 264.7 cells by 49.75% at 1000 µg/mL. LD50 (lethal dose 50%) was estimated at around 2000 mg/kg (i.p.). HE-02 reduced Ehrlich tumor cell viability and peritumoral microvessels density. There was an increase of Th1 helper T lymphocytes cytokine profile levels (IL-1β, TNF-α, IL-12) and a decrease of Th2 cytokine profile (IL-4, IL-10). Moreover, an increase was observed on reactive oxygen species and nitric oxide production. Weak in vivo toxicological effects were recorded. Our data provide evidence that the piperine analogue HE-02 present low toxicity, and its antitumor effect involves modulation of immune system to a cytotoxic Th1 profile.

SB-83, a 2-Amino-thiophene derivative orally bioavailable candidate for the leishmaniasis treatment

Leishmaniasis, affecting more than 12 million people worldwide has become a severe public-health problem. The therapeutic arsenal against leishmaniasis is mainly administered by parenteral route; it is toxic, expensive, and associated with recurrence risk. The need for further therapeutic compounds research is pressing. In previous studies, we demonstrated the antileishmanial activities of ten 2-amino-thiophene derivatives, which evidenced the action of a compound, called SB-83, having expressive antileishmania activity in an in vitro infection model. In the present work, we describe preclinical studies of the thiophenic derivative SB-83, such as acute toxicity, genotoxicity, in vivo oral efficacy in a murine model, and in vitro antileishmanial activity against an L. amazonensis SbIII-resistant strain. Determining acute preclinical toxicity, the LD50 of SB-83 was estimated at 2500 mg/kg orally, with few behavioral changes in Swiss mice. Further, treatment with 2000 mg/kg of SB-83 did not induce in vivo genotoxic activity in the peripheral blood micronucleus assay. In 7 weeks of oral treatment, SB-83 reduced paw lesion size in L. amazonensis infected mice by 52.47 ± 5.32%, and decreased the parasite load of the popliteal lymph node and spleen at the highest dose tested (200 mg/kg) respectively by 42.57 ± 3.14%, and 100%, without presenting weight change or other changes of clinical importance in the biochemical and hematological profiles. The treatment of promastigotes and intracellular amastigotes of SbIII sensitive and resistant strains with SB-83 did not produce differences in antileishmania activity, which suggests no cross-resistance. Thus, this work demonstrated that SB-83 has potential as a new active drug candidate even when orally administered, which may become a new therapeutic alternative for the treatment of leishmaniasis.

Brown Algae Padina sanctae-crucis Børgesen: A Potential Nutraceutical

Padina sanctae-crucis Børgesen is distributed worldwide in tropical and subtropical seas; belongs to the Dictyotaceae family, and has proven to be an exceptional source of biologically active compounds. Four compounds were isolated and identified, namely: dolastane diterpene new for the genus Padina; phaeophytin and hidroxy-phaeophytin new for the family Dictyotaceae, and; mannitol first described in this species. Saturated fatty acids as compared to the percentages of unsaturated fatty acids were shown to be present in greater abundance. Palmitic and linolenic acid were the main saturated and unsaturated acids, respectively. Cytotoxic and antioxidant activities were evaluated using human erythrocytes. In vivo evaluations of acute toxicity and genotoxicity were performed in mice. Methanolic extract of P. sanctae-crucis presented antioxidant activity and did not induce cytotoxicity, genotoxicity or acute toxicity. Since Padina sanctae-crucis is already used as food, has essential fatty acids for the nutrition of mammals, does not present toxicity and has antioxidant activity, it can be considered as a potential nutraceutical.