Nephroprotective effects of Lippia sidoides ethanolic extract against ischemia/reperfusion-induced acute kidney injury

Abstract Ischemia/reperfusion injury (I/R) is commonly related to acute kidney injury (AKI) and oxidative stress. Antioxidant agents are used to treat this condition. Lippia sidoides is a brazillian shrub with anti-inflammatory and anti-oxidative properties. Thus, the aim of this study is to evaluate the effect of Lippia sidoides ethanolic extract (LSEE) on in vivo and in vitro models of AKI induced by I/R. Male Wistar rats were submitted to unilateral nephrectomy and ischemia on contralateral kidney for 60 min via clamping followed by reperfusion for 48 h. They were divided into four groups: Sham, LSEE (sham-operated rats pre-treated with LSEE), I/R (rats submitted to ischemia) and I/R-LSEE (rats treated with LSEE before ischemia). Kidney tissues homogenates were used to determine stress parameters and nephrin expression. Plasma and urine samples were collected for biochemical analysis. I/R in vitro assays were evaluated by 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and flow cytometry assays in Rhesus Monkey Kidney Epithelial Cells (LLC-MK2). The LSEE treatment prevented biochemical and nephrin expression alterations, as well as oxidative stress parameters. In the in vitro assay, LSEE protected against cell death, reduced the reactive oxygen species and increased mitochondrial transmembrane potential. LSEE showed biotechnological potential for a new phytomedicine as a nephroprotective agent.

Agrobacterium rhizogenes-mediated transformation of Hypericum sinaicum L. for the development of hairy roots containing hypericin

Hypericum sinaicum L. is an endangered Egyptian medicinal plant of high importance due to the presence of naphthodianthrones (hypericins), which have photodynamic properties and pharmaceutical potential. We sought to assess H. sinaicum ability to develop hairy roots that could be cultured in contained conditions in vitro and used as a source for hypericin production. We used four A. rhizogenes strains differing in their plasmids and chromosomal backgrounds to inoculate excised H. sinaicum root, stem and leaf explants to induce hairy root development. Additionally, inoculum was applied to shoots held in Rockwool cubes supporting their stand after removal of the root system. All explant types were susceptible to A. rhizogenes although stem explants responded more frequently (over 90%) than other explant types. The A4 and A4T A. rhizogenes strains were highly, and equally effective in hairy root induction on 66-72% of explants while the LBA1334 strain was the most effective in transformation of shoots. Sonication applied to explants during inoculation enhanced the frequency of hairy root development, the most effective was 60 s treatment doubling the percentage of explants with hairy roots. However, shoot transformation was the most effective approach as shoots developed hairy roots within 10 days after inoculation. Molecular analyses confirmed that the established hairy root cultures in vitro were indeed obtained due to a horizontal gene transfer from bacteria. These cultures grew fast and the hypericin content in hairy roots was about two fold higher than in H. sinaicum plants as determined by HPLC.

Analgesic effect of Hypericum perforatum, Valeriana officinalis and Piper methysticum for orofacial pain

To evaluate in vivo the association of hypericum Hypericum perforatum, valerian Valeriana officinalis and kava Piper methysticum with analgesia by assessing their effects in reducing orofacial pain as well as the possible hepatic, hematologic and biochemical alterations induced by regular administration of these extracts. METHODS: Orofacial pain was induced in mice with the administration of 2.5% formalin in the upper lip. After 60 min, the animals were treated with saline, carbamazepine and hydroalcoholic plant extracts. The nociceptive intensity was determined by the timing at which the animal remained rubbing the injected area. To assess the hepatotoxic effect, mice were chronically treated for 25 days with saline, carbamazepine and hydroalcoholic extract. The animals were euthanized and the liver weighed, followed by a differential count of leukocytes and measurement of alanine transaminase and alkaline phosphatase. RESULTS: The evaluation of analgesic activity in phase 1 reduced the time of rubbing compared to the control by 86% 0.05 mL/10 g and 76% 0.10 mL/10 g. In phase 2, the extracts reduced rubbing time by 94% and 85%, respectively. In the evaluation of alkaline phosphatase, the groups treated with extracts at doses of 0.05 mL/10 g and 0.1 mL/10 g increased by 16.1% and 9.5% compared to the control group and a reduction of 8.5% and 9.1% in the evaluation of alanine transaminase respectively. It was demonstrated that in the differential counts showed an increase in eosinophils in the treated group with 0.05 mL/10 g. CONCLUSIONS: The use of hydroalcoholic extract of the associated plants reduced the orofacial formalin-induced pain with better results than carbamazepine, at both the neural conductor level of pain phase 1 and in inflammatory or later pain phase 2 without presenting hepatotoxicity. The observed eosinophilia is suggestive of a phenomenon called hormesis...

Hepatotoxicidade induzida por Hypericum perforatum com possível associação a copaíba (Copaifera langsdorffii Desf): relato de caso / Hypericum perforatum-induced hepatotoxicity with possible association with copaiba (Copaifera langsdorffii Desf):case report

Relatamos um caso de dano hepático em paciente idosa após uso de produtos naturais à base de Hypericum perforatum e copaíba (Copaifera langsdorffii Desf). A hepatotoxicidade do Hypericum perforatum é conhecida por relatos, mas a respeito da copaíba, largamente usada como anti-inflamatório, há apenas dados experimentais na literatura nacional. Essa apresentação visou chamar a atenção para possível efeito tóxico dessa associação, bem como para a recuperação clínica da paciente após interrupção de seu uso. Há uma tendência de suspeitar sobre a ação de medicamentos para justificar a lesão hepática aguda não viral, em razão do grande número de fármacos responsáveis por hepatotoxicidade. A literatura tem publicado experimentos e relatos clínicos em que produtos fitoterápicos, inclusive Hypericum perforatum, são o agente causador dessa agressão, considerados inócuos e utilizados livremente. É preciso lembrar que reações adversas ocorrem também com essas substâncias, merecendo sua investigação na obtenção da anamnese, pela possibilidade de promoverem quadros graves de falência hepática.

We report a case of liver damage in an elderly patient after the use of herbal products of Hypericum perforatum and copaiba (Copaifera langsdorffii Desf). Hepatotoxicity related to Hypericum perforatum is anecdotally known, but for copaiba, widely used as anti-inflammatory, there is just experimental data in the national literature. This report aimed to draw attention to the possible toxic effects of this association as well as to the clinical recovery of the patient after discontinuing their use. There is a tendency to suspect of the action of drugs to justify a non-viral acute liver injury, because of the large number of drugs responsible for hepatotoxicity. There are experiments and clinical reports in the literature describing some herbal products, including Hypericum perforatum, as the causative agents of this aggression, and are considered innocuous and used with no restrictions. We must remember that adverse reactions also occur with these substances; hence, they should be investigated when collecting the patient´s history, for leading to severe liver failure.