Pharmacological evaluation of a traditional Brazilian medicinal plant, Monteverdia ilicifolia. Part I - Preclinical safety study.

ETHNOPHARMACOLOGICAL RELEVANCE: Monteverdia ilicifolia (Maytenus ilicifolia, Celastraceae), known as "espinheira-santa", has been widely used in Brazil to manage mainly gastrointestinal diseases. This species has been listed in the Brazilian Pharmacopeia and in the National List of Essential Medicines (RENAME). Considering that clinical studies about M. ilicifolia are rare, our group has been performing a broader project designed to evaluate the efficacy of M. ilicifolia capsules in a clinical trial, for this reason, approaches to provide safety to those patients are relevant. AIM OF THE STUDY: We aimed to investigate the potential pharmacokinetic interaction and hepatotoxicity and intestinal toxicity of an aqueous extract of M. ilicifolia and its main phytocompounds, catequin, epicatequin, and quercetin. METHODS AND MATERIALS: Slices of liver and intestine of Wistar rats were incubated with different concentrations of M. ilicifolia extract or isolated compounds (catechin, epicatechin and quercetin). Commercial kits were used to evaluate enzyme activities of CYP2D6 and CYP3A4 isoforms, as well as cell viability (MTT) assay and intracellular enzymes leakage, specifically lactate dehydrogenase (LDH), alkaline phosphatase (AP), aspartate aminotransferase (AST), alanine aminotransferase (ALT) were studied. RESULTS: Incubation with M. ilicifolia extract, catechin, epicatechin and quercetin did not affect significantly any evaluated parameter in intestines. The intracellular enzymes leakages, CYP2D6, LDH and AST, were increased with M. ilicifolia extract and quercetin in liver slices. CONCLUSIONS: Our in vitro findings highlighted, for the first time, the potential hepatotoxicity induced by an aqueous extract of M. ilicifolia, consequently this species and its products should be avoided in liver diseases, supporting that studies of safety must be performed including in the context of traditional medicinal plants.

Achyrocline satureioides as an adjuvant therapy for the management of mild viral respiratory infections in the context of COVID-19: Preliminary results of a randomized, placebo-controlled, and open-label clinical trial.

We evaluated the impact of an Achyrocline satureioides inflorescence infusion on the clinical outcomes of viral respiratory infections, including those caused by SARS-CoV-2, in a monocentric, randomized, open-label, placebo-controlled clinical trial. Patients with symptoms of viral respiratory infection, including suspected cases of COVID-19, were included and assigned to receive either A. satureioides (n = 57) or Malus domestica (n = 67) infusions twice a day for 14 days. All participants were included before the RT-PCR results, performed using a nasopharyngeal swab. The patients were further divided into subgroups according to real-time polymerase chain reaction results: SARS-CoV-2-positive and SARS-CoV-2-negative subgroups for statistical analyses. We assessed clinical outcomes, such as the latency to resolution of cough, dyspnea, fever, sore throat, chest pain, smell and taste dysfunctions, diarrhea, nausea, abdominal pain, and loss of appetite; hospitalization; and mortality with questionnaires and medical records. The subjects that received early A. satureioides infusion showed a significant reduction in the average number of days with respiratory and neurological symptoms compared with the control group (M. domestica infusion). We conclude that A. satureioides is a safe agent and, in combination with standard care, improves viral respiratory infection symptoms, especially those related to COVID-19.

Achyrocline satureioides review: From the pharmacochemical diversity to the technological development of products.

Achyrocline satureioides (Lam.) DC (Asteraceae) is a native species of the southeastern subtropical and temperate region of South America, popularly known as "marcela" or "macela". This species is recognized, in traditional medicine, by diverse biological activities such as digestive, antispasmodic, anti-inflammatory, antiviral, sedative, hepatoprotective, among others. Some of these activities have been related to the presence of phenolic compounds, including flavonoids, phenolic acids, terpenoids in the essential oils, coumarins and phloroglucinol derivatives reported to the species. The approaches on the technological development of phytopharmaceutical products of this species provided relevant advances in the optimization of the extraction and product obtention, especially spray-dried powders, hydrogels, ointments, granules, films, nanoemulsions and nanocapsules. The most relevant biological activities described for the extracts or derivative products from A. satureioides were antioxidant, neuroprotective, antidiabetic, antiobesity, antimicrobial, anticancer effects, and obstructive sleep apnea syndrome. The scientific and technological findings reported for the species, in conjunction with its traditional use and cultivation, reveal the high potential of the species for diverse industrial applications.

Iridoids as a Potential Hepatoprotective Class: A Review.

BACKGROUND: Liver disease rates are gradually increasing over the years, becoming a severe public health problem. The indiscriminate use of drugs associated with a rich fat diet, high consumption of alcoholic beverages, and exposure to viral infections and lipid peroxidative products are considered the chief factors for developing hepatic disorders. Owing to the absence of reliable hepatoprotective drugs in the therapeutic arsenal, since they present a high incidence of adverse reactions and/or lack of efficacy in some cases, liver diseases are widely treated with medicinal plants. Among them are the plants producing iridoids, which are believed to be good remedies for liver disease due to their bitter taste. The hepatoprotective effect of iridoids and extracts, rich in these compounds, has been demonstrated, both in vitro and in vivo. OBJECTIVE: This review aims to scrutinize the available literature related to the hepatoprotective activity of iridoids. METHODS: The information was obtained from scientific databases (Science Direct, PubMed, Web of Science, Scopus, ACS Publications, Wiley Online Library) until December, 2021. RESULTS AND CONCLUSION: A total of 63 hepatoprotective iridoids were found, including aucubin, catalpol and picroliv, a mixture of two iridoids. They are the target of a high number of studies, which revealed their protective action against different hepatotoxic agents and detailed action mechanisms.

Subtribe Hyptidinae (Lamiaceae): A promising source of bioactive metabolites.

ETHNOPHARMACOLOGICAL RELEVANCE: The subtribe Hyptidinae contains approximately 400 accepted species distributed in 19 genera (Hyptis, Eriope, Condea, Cantinoa, Mesosphaerum, Cyanocephalus, Hypenia, Hyptidendron, Oocephalus, Medusantha, Gymneia, Marsypianthes, Leptohyptis, Martianthus, Asterohyptis, Eplingiella, Physominthe, Eriopidion and Rhaphiodon). This is the Lamiaceae clade with the largest number of species in Brazil and high rates of endemism. Some species have been used in different parts of the world mainly as insecticides/pest repellents, wound healing and pain-relief agents, as well as for the treatment of respiratory and gastrointestinal disorders. AIM OF THE REVIEW: This review aims to discuss the current status concerning the taxonomy, ethnobotanical uses, phytochemistry and biological properties of species which compose the subtribe Hyptidinae. MATERIALS AND METHODS: The available information was collected from scientific databases (ScienceDirect, Pubmed, Web of Science, Scopus, Google Scholar, ChemSpider, SciFinder ACS Publications, Wiley Online Library), as well as other literature sources (e.g. books, theses). RESULTS: The phytochemical investigations of plants of this subtribe have led to the identification of almost 300 chemical constituents of different classes such as diterpenes, triterpenes, lignans, α-pyrones, flavonoids, phenolic acids and monoterpenes and sesquiterpenes, as components of essential oils. Extracts, essential oils and isolated compounds showed a series of biological activities such as insecticide/repellent, antimicrobial and antinociceptive, justifying some of the popular uses of the plants. In addition, a very relevant fact is that several species produce podophyllotoxin and related lignans. CONCLUSION: Several species of Hyptidinae are used in folk medicine for treating many diseases but only a small fraction of the species has been explored and most of the traditional uses have not been validated by current investigations. In addition, the species of the subtribe appear to be very promising as alternative sources of podophyllotoxin-like lignans which are the lead compounds for the semi-synthesis of teniposide and etoposide, important antineoplastic agents. Thus, there is a wide-open door for future studies, both to support the popular uses of the plants and to find new biologically active compounds in this large number of species not yet explored.

Hypericum species: An analysis on the patent technologies.

Hypericum (Hypericaceae) is a genus that comprises approximately 500 species around the world. The industrial relevance of these plants is based on the occurence of specialized metabolites that exhibit a range of pharmaceutical potential. Besides that, several species are relevant due to their ornamental value. Taking to account the vast market worth of products and processes involving Hypericum, the present study aims to provide a comprehensive overview of patents concerning this subject between 2007and 2017. For this purpose, a survey was performed in free databases (Espacenet®, PatentScope® and Google Patents®) using the keyword Hypericum in the patents title or title plus abstract. The documents were then organized by groups (medicinal and non-medicinal approaches), subgroups, type of applicants and countries. Espacenet® was chosen to data analysis, and a total of 174 patents were found. The majority of the applicants are from China and companies appear as the principal owners of patents. Several technologies are not intended for medicinal purposes, being mainly related to the development of new cultivars for ornamental uses. Concerning the medicinal approaches, the chief subject is related to extraction and incorporation into formulations. The main species cited in the documents is H. perforatum and the therapeutic use is for central nervous system diseases. In general, this study covers the patents published in recent years hoping to boost the scientists and companies that invest in Hypericum researches to visualize the state of art, opportunities and challenges for innovation in this area.

Structural diversity and biological activities of phloroglucinol derivatives from Hypericum species.

Plants of the genus Hypericum (Hypericaceae) are used in folk medicine all over the world, H. perforatum being the most well-known species. Standardized extracts of this plant are commercially-available to treat mild to moderate depression cases. The present review summarizes the literature published up to 2016 concerning the phloroglucinol derivatives isolated from Hypericum species, together with their structural features and biological activities. These phytochemical studies led to the isolation of 101 prenylated phloroglucinols, chromanes and chromenes, 35 dimeric acylphloroglucinols, 235 polycyclic polyprenylated acylphloroglucinols, 25 simple benzophenones and 33 phloroglucinol-terpene adducts. These compounds show a diverse range of biological activities, such as antimicrobial, cytotoxic, antinociceptive and antidepressant-like effects.

Denudatin A, a Dimeric Acylphloroglucinol from Hypericum denudatum Presents an Antinociceptive Effect in Mice.

A new dimeric acylphloroglucinol, denudatin A (1), was isolated from the flowering aerials parts of Hypericum denudatum, along with the known phloroglucinols selancin A (2), hyperbrasilol A (3), uliginosin B (4), and isouliginosin B (5). The structure of 1 was elucidated using 1D, 2D NMR, and MS experiments, and by comparison with previously reported data for Hypericum dimeric acylphloroglucinols. Denudatin A (1) and selancin A (2) were administered orally to mice displaying antinociceptive activity in the hot plate test. The compounds did not induce motor impairment in the rotarod apparatus.

Dimeric acylphloroglucinols from Hypericum austrobrasiliense exhibiting antinociceptive activity in mice.

Three dimeric acylphloroglucinols, austrobrasilol A, austrobrasilol B and isoaustrobrasilol B were isolated from the flowers of Hypericum austrobrasiliense (Hypericaceae, section Trigynobrathys). Their structures were elucidated using mass spectrometry and NMR experiments (1D and 2D), and by comparison with previously reported data for other dimeric acylphloroglucinols isolated from Hypericum and Elaphoglossum genera. The three compounds were orally administered in mice at equimolar doses to uliginosin B (15mg/kg, p.o.) displaying antinociceptive activity in the hot-plate test. The compounds did not induce motor impairment in the rotarod apparatus.

Chemical constituents and pharmacological profile of Gunnera manicata L. extracts

Gunnera perpensa L. (Gunneraceae) is a native South African plant widely used in traditional medicine as an antibacterial and antifungal. In southern Brazil there is the native species called Gunnera manicata L. that also belongs to the Gunneraceae. Nevertheless, there is no information about chemical and pharmacological properties of South American Gunnera species. Therefore this study aimed at assessing the phytochemical and pharmacological profiles of aqueous and methanol Brazilian G. manicata extracts. The results showed that antimicrobial activity in an agar diffusion assay was effective against Staphylococcus aureus and Candida albicans . Phenolic compounds were investigated by liquid chromatography coupled with a tandem mass spectrometer (LC-MS/MS) and all extracts presented gallic acid and only the methanol extract obtained from the leaves exhibited hyperoside. Rutin, quercetin and chlorogenic acid were not found in the samples analysed. Total phenolic content was higher in methanol extract and total flavonoid content was low in all extracts. Antioxidant activity was evaluated by the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) radical test, and all samples presented good to moderate antioxidant activity. These results encourage complementary studies on the chemical composition of the plant extracts focusing on isolation and structure elucidation of their active compounds.

Gunnera perpensa L. (Gunneraceae) é uma planta nativa do sul da África utilizada na medicina tradicional como antibiótico e antifúngico. Gunnera manicata L. é uma planta nativa do sul do Brasil também da família Gunneraceae e, apesar disso, não há informações sobre suas propriedades químicas e farmacológicas. Assim, o objetivo deste estudo foi avaliar o perfil fitoquímico e farmacológico dos extratos aquoso e metanólico de G. manicata. Os resultados do ensaio microbiológico de difusão em ágar demonstraram que os extratos testados foram ativos contra Staphylococcus aureus e Candida albicans. A presença de compostos fenólicos foi investigada pela técnica de Cromatografia Líquida acoplada a espectrômetro de massas em Tandem (CL-EM/EM). Em todas as amostras analisadas verificou-se a presença de ácido gálico e somente o extrato metanólico das folhas apresentou hiperosídeo. Rutina, quercetina e ácido clorogênico não foram encontrados. O conteúdo total de compostos fenólicos foi maior nos extratos metanólicos e o conteúdo de flavonóides totais foi baixo em todos os extratos. A atividade antioxidante foi avaliada pelo teste da atividade do radical 2,2-diphenyl-1-picril-hidrazil (DPPH) e todas as amostras apresentaram boa a moderada atividade antioxidante. Esses resultados encorajam estudos complementares da composição química dos extratos com foco no isolamento e na elucidação estrutural dos compostos ativos.