Antimicrobial Activity and Synergy Investigation of Hypericum scabrum Essential Oil with Antifungal Drugs

The chemical composition of Lebanese Hypericum scabrum essential oil (EO) was analyzed by gas chromatography (GC) and gas chromatography-mass spectrometry (GG-MS). Its antimicrobial activity was evaluated by determining its minimal inhibitory concentrations (MICs) against a Gram-negative and a Gram-positive bacterium, one yeast, and five dermatophytes. H. scabrum EO was most active on filamentous fungi (MIC values of 32–64 µg/mL). Synergy within the oil was investigated by testing each of the following major components on Trichophyton rubrum: α-pinene, limonene, myrcene, β-pinene and nonane, as well as a reconstructed EO. The antifungal activity of the natural oil could not be reached, meaning that its activity might be due, in part, to minor constituent(s). The interactions between H. scabrum EO and commercially available antifungals were assessed by the checkerboard test. A synergistic effect was revealed in the combination of the EO with amphotericin B.

AÇÃO ANTIMICROBIANA DE ÓLEOS DE SEMENTES FRENTE A CEPAS DE STAPHYLOCOCCUS AUREUS

Introdução: O crescente aumento da resistência bacteriana frente a múltiplas drogas se deve ao uso indiscriminado de antibióticos e tem causado preocupações quanto ao tratamento de doenças infecciosas em humanos e animais. Neste sentido, uma das bactérias que merece destaque, por conta de sua resistência a antibióticos, ampla incidência e alto potencial de contágio entre humanos e animais é o Staphylococcus aureus. Diante disso, buscam-se alternativas para o tratamento de doenças de origem infecciosa, as quais sejam eficazes, porém sem aumentar a resistência bacteriana. Deste modo, os óleos vegetais são um exemplo viável, tendo em vista sua disponibilidade, baixo preço e presença de compostos bioativos com efeitos antimicrobianos que não induzem resistência bacteriana. Objetivo: realizar uma revisão da literatura acerca de óleos obtidos a partir de sementes e sua ação antimicrobiana frente a S. aureus. Método: Foi realizada uma revisão da literatura por meio do banco de dados Scholar Google, no qual foram selecionados trabalhos entre os anos de 2011 e 2021 com um nº de 31, cujas palavras-chave utilizadas foram: "seed oil", "antimicrobial" e "S. aureus". Resultados: Os métodos mais utilizados para avaliação da atividade antimicrobiana foram Difusão em poço, Concentração Inibitória Mínima e Concentração Bactericida Mínima. Os óleos encontrados foram os da semente de Azadirachta indica, Laurus nobilis, Linum usitatissimum, Citrus sinensis, Mangifera indica, Capsicum frutescens, Capsicum frutescens, Cucurbita moschata, Syagrus coronata, Cucurbita argyrosperma, Hypericum scabrum, entre outros. Em todos os estudos foram verificados efeitos antimicrobianos frente a S. aureus, inclusive alguns relataram tal efeito em cepas resistentes à Meticilina (MRSA), como é o caso dos óleos de Nigella sativa, Myristica fragrans e Syagrus coronata. Além disso, esses efeitos foram atribuídos ao teor de ácidos graxos encontrados nos óleos, compostos esses capazes de interferir na membrana celular bacteriana degenerando-a. Alguns estudos ainda relataram que a atividade antibacteriana dos óleos depende da correlação com a concentração dos principais compostos ativos, indicando a necessidade de isolamento dos mesmos. Conclusão: Os óleos obtidos a partir de sementes demonstram efeitos antimicrobianos apreciáveis e, portanto, estudos farmacológicos são necessários para um melhor entendimento acerca de seu mecanismo de ação.

STUDY OF THE PROCESS EXTRACTION OF HYPERICIN FROM THE AERIAL PARTS OF HYPERICUM SCABRUM AND HYPERICUM PERFORATUM

The process extraction of hypericin from the aerial parts of Hypericum scabrum and Hypericum perforatum was studied. On the basis results research, the following extraction conditions were established: extractant – 80% ethanol, particle size of raw material – no more than 8 mm and process temperature – 20–40 °C. By the method of mathematical planning of the experiment according to Box-Wilson, the extraction conditions were determined, which ensure the extraction of hypericin from the raw material with a yield of 95%. Proposed a five-fold extraction of hypericin from the aerial parts of H. scabrum and H. perforatum with the necessary infusion at the first contact of the phases – 6 hours, at the second – 5 hours, at the third and fourth – 4 hours and at the fifth – 2 hours. The proposed a united technology for obtaining a «Dry extract of Hypericum» from the aerial parts of H. perforatum and H. scabrum. The proposed conditions for the extraction of hypericin were tested at the Technology center for GMP requirements by the Institute of the Chemistry of Plant Substances, of the Academy of Sciences Republic of Uzbekistan. More than 500.0 kg of the substance «Dry extract of Hypericum» adequate of Technical Conditions 03535440-022: 2016 has been produced.

Unusual derivatives from Hypericum scabrum

Three new compounds (1–3) with unusual skeletons were isolated from the n-hexane extract of the air-dried aerial parts of Hypericum scabrum. Compound 1 represents the first example of an esterified polycyclic polyprenylated acylphloroglucinol that features a unique tricyclo-[4.3.1.11,4]-undecane skeleton. Compound 2 is a fairly simple MPAP, but with an unexpected cycloheptane ring decorated with prenyl substituents, and compound 3 has an unusual 5,5-spiroketal lactone core. Their structures were determined by extensive spectroscopic and spectrometric techniques (1D and 2D NMR, HRESI-TOFMS). Absolute configurations were established by ECD calculations, and the absolute structure of 2 was confirmed by a single crystal determination. Plausible biogenetic pathways of compounds 1–3 were also proposed. The in vitro antiprotozoal activity of the compounds against Trypanosoma brucei rhodesiense and Plasmodium falciparum and cytotoxicity against rat myoblast (L6) cells were determined. Compound 1 showed a moderate activity against T. brucei and P. falciparum, with IC50 values of 3.07 and 2.25 μM, respectively.

Hypolipidemic effects of Hypericum Scabrum extract on the serum lipid profile and obesity in high-fat diet fed rats

Diets included high-fat (HFD) and high calories intake is correlated with greater risk of obesity and oxidative stress, which lead to increase the risk of related diseases such as cardiovascular and metabolic disease. In the present study, we have examined the hypolipidemic activity of Hypericum Scabrum extract on HFD fed rats. Fifty-four male Wistar rats divided into six groups: 1) control, 2) H. Scabrum extract (100 mg/kg gavage per day), 3) H. Scabrum extract (300 mg/kg), 4) HFD, 5) HFD and H. Scabrum extract (100 mg/kg), 6) HFD and H. Scabrum extract (300 mg/kg). The groups were fed their diet and treatment for 3 months. Biochemical analysis showed elevated lipid serum profile in HFD rats compared to control group. H. Scabrum extract supplementation significantly ameliorated triglyceride, total cholesterol and LDL-cholesterol. H. Scabrum extract supplementation leading to increase HDL-cholesterol in HFD treated groups. This experiment showed that H. Scabrum extract decreased HFD complications and might be beneficial herbal drug for treatment of hyperlipidemia and obesity.