Investigation of the role of rosmarinic acid treatment in regulating inflammation, cell damage, and angiogenesis in rat ovarian torsion and detorsion models

Abstract Purpose To investigate the protective effect of rosmarinic acid (RA) in ovarian ischemia/reperfusion injury using biochemical, histopathological, and immunohistochemical methods. Methods Wistar female rats (n = 32) were randomly divided into four groups: control, ischemia, ischemia-reperfusion, and ischemia-reperfusion with RA. Rosmarinic acid was given at a dose of 50 mg/kg by oral gavage three hours after reperfusion. Malondialdehyde (MDA) levels and glutathione peroxidase (GSH-Px) activities were determined in the ovary tissue homogenates for each rat. Results In the ischemia-reperfusion with RA group, the epithelial cells are regularly regulated at the periphery, and the degenerative changes in preantral and antral follicle cells are reduced. Follicle cells and cells in the corpus luteum showed a decrease in vascular endothelial growth factor (VEGF) expression, while VEGF demonstrated a positive reaction in vascular endothelial cells and stromal cells. The TNF-α expression due to the decreased degenerative effect and inflammation was positive in the macrophage cells. The expression of caspase-3 as an apoptosis change was negative in antral follicle cells and granular cells around the antral follicle. Conclusion Different doses of RA may be useful in preventing ischemic damage after vascularization, inflammation, and apoptotic development after ischemia/reperfusion.

Does rosmarinic acid underestimate as an experimental cardiovascular drug? / Seria o ácido rosmarínico subestimado como droga cardiovascular experimental?

PURPOSE: The rationale of the present review is to analize the activity of Rosmarinus officinalis in the the cardiovascular system METHODS: A MEDLINE database search (from January 1970 to December 2011) using only rosmarinic acid as searched term. RESULTS: The references search revealed 509 references about rosmarinic acid in 40 years (the first reference is from 1970). There is a powerful prevalence of antioxidant and cancer studies. Other diseases are few cited, as inflammation, brain (Alzheimer and Parkinson disease) and, memory; allergy; diabetes; atherosclerosis, and; hypertension. It is necessary to consider the complete absence of studies on coronary artery disease, myocardial ischemia, heart failure or ischemia/reperfusion injury. CONCLUSION: Rosmarinic acid is underestimated as an experimental cardiovascular drug and deserves more attention.

OBJETIVO: A justificativa da revisão é analisar a atividade de Rosmarinus officinalis no sistema cardiovascular MÉTODOS: Uma busca de banco de dados MEDLINE (de janeiro de 1970 a dezembro de 2011), utilizando apenas o ácido rosmarínico como termo pesquisado. RESULTADOS: A busca referências revelou 509 referências sobre o ácido rosmarínico em 40 anos (a primeira referência é de 1970). Há uma prevalência poderoso antioxidante e estudos do câncer. Outras doenças são citados alguns, como o cérebro, inflamação (de Alzheimer e doença de Parkinson) e, a memória, hipertensão, alergia, diabetes, aterosclerose, e. É necessário ter em conta a ausência completa de estudos sobre a doença de artéria coronária, isquemia do miocárdio, insuficiência cardíaca ou isquemia / lesão de reperfusão. CONCLUSÃO: O ácido rosmarínico é subestimado como uma droga experimental cardiovascular e merece mais atenção.

Protective activity of picroliv on hepatic amoebiasis associated with carbon tetrachloride toxicity.

BACKGROUND AND OBJECTIVE: Picroliv, isolated from the root and rhizome of Picrorhiza kurroa, is known to have significant hepatoprotective activity. Its effects against Entamoeba histolytica induced liver damage are not studied. This study aims to evaluate the hepatoprotective action of picroliv against the hepatotoxic changes induced by carbon tetrachloride (CCl(4)) and E. histolytica infection in three animal models. METHODS: Mastomys, gerbils and albino Druckray rats were used in this study. A total of 30 animals were used for each model and divided into five groups of six animals each. Group I consisted of normal animals. The rest received six doses of CCl(4) intraperitoneally. Group II served as hepatotoxic control. The remaining animals were infected intraperitoneally with E. histolytica trophozoites, of which group III was the hepatotoxic plus amoeba infected control. The remaining animals were divided into two groups, one received hepatoprotective agent picroliv and the other silymarin. All animals were sacrificed seven days post amoeba infection. RESULTS: Increase in the enzyme levels induced by CCl(4) was further elevated after E. histolytica infection. Pinpoint abscesses were found to develop only in gerbils after E. histolytica infection. Picroliv was found to possess hepatoprotective activity against amoebic liver abscess. INTERPRETATION AND CONCLUSION: Significant recovery obtained in serum enzyme levels in all animal models and against amoebic liver abscess in gerbils on treatment with picroliv indicated that picroliv possesses therapeutic activity against E. histolytica induced hepatic damage.

Prevention of carbon tetrachloride-induced hepatic injury in mice by Picrorhiza kurrooa.

OBJECTIVE: Picrorhiza kurrooa (Pk) has been used in liver diseases in the Indian indigenous system of medicine. We undertook this study to determine whether Pk extract possesses hepatoprotective function and if so to determine its nature and mechanism. METHODS: Liver injury was induced in 16 mice by thrice-a-week injection of carbon tetrachloride (CCl4) for nine weeks. Eight of them were given daily feeding of Pk extract (12 mg/Kg) 10 days prior to CCl4 injection. Control mice (n = 6) were injected with olive oil for the same period. Serum markers of liver injury and histology of liver tissues were studied. Hepatic glutathione (GSH), total thiol (-SH), glucose 6-phosphate dehydrogenase (G6PD), catalase, lipid peroxidation and plasma membrane-bound Na+/K+ ATPase were also determined. RESULTS: CCl4 treatment resulted in significant elevation of serum ALT and AST. Liver GSH [6.3 (0.7) vs control 10.5 (1.1) micrograms/mg protein], -SH, G6PD, catalase and membrane-bound Na+/K+ AT-Pase [164.3 (23.2) vs control 358.4 (12.9) nmole pi released/min/mg protein] were significantly reduced. Significant increase of lipid peroxidation [3.0 (0.6) vs control 1.0 (0.3) nmole MDA/mg protein] and histologic changes characteristic of liver injury were also seen. Feeding of Pk extract in CCl4-treated mice caused significantly less alteration of serum ALT, AST, liver GSH [8.9 (0.7) micrograms/mg protein], -SH, G6PD, catalase and membrane-bound Na+/K+ ATPase [270.8 (21.3) nmole pi released/min/mg protein]. Histologic lesions of liver and lipid peroxidation [1.7 (0.4) nmole MDA/mg protein] were also significantly less in these animals. CONCLUSION: The extract of Pk appears to offer significant protection against liver damage by CCl4. It probably acts as free-radical scavenger and inhibitor of lipid peroxidation of liver plasma membrane.

Anticholestatic effect of picroliv, active hepatoprotective principle of Picrorhiza kurrooa, against carbon tetrachloride induced cholestasis.

Picroliv showed a dose (3-12 mg/kg, po for 7 days) dependent choleretic activity as evidenced by increase in bile flow and its contents (bile salts and bile acids). Significant anticholestatic activity was also observed against carbon tetrachloride induced cholestasis in conscious rat, anaesthetized guinea pig and cat. Picroliv was more active than the known hepatoprotective drug silymarin.

In vitro studies on the effect of certain natural products against hepatitis B virus.

Picroliv (active principle from Picrorrhiza kurroa), its major components picroside I, catalpol, kutkoside I, kutkoside, andrographolide (active constituent of Andrographis paniculata), silymarin and Phyllanthus niruri extract were tested for the presence of anti hepatitis B virus surface antigen (anti HBs) like activity. HBsAg positive serum samples obtained from hepatitis B virus (HBV) associated acute and chronic liver diseases and healthy HBsAg carriers were used to evaluate the anti-HBs like activity of compounds/extract. The latter were mixed with serum samples and incubated at 37 degrees C overnight followed by HBsAg screening in the Elisa system. A promising anti-HBsAg like activity was noted in picroliv (and its major components) catalpol, P. niruri which differed from the classical viral neutralization. Picroliv also inhibited purified HBV antigens (HBsAg and HBsAg) prepared from healthy HBsAg carriers. The in vitro testing system appears to be a suitable model to identify an agent active against HBV, prior to undertaking detailed studies.

Evaluation of hepatoprotective activity of picroliv (from Picrorhiza kurroa) in Mastomys natalensis infected with Plasmodium berghei.

Administration of picroliv, a standardized fraction of alcoholic extent of Picrorhiza kurroa (3-12 mg/kg/day for two weeks) simultaneously with P. berghei infection showed significant protection against hepatic damage in Mastomys natalensis. The increased levels of serum glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), alkaline phosphatase, lipoprotein-X (LP-X) and bilirubin in the infected animals were marked reduced by different doses of picroliv. In the liver, picroliv decreased the levels of lipid peroxides and hydroperoxides and facilitated the recovery of superoxide dismutase and glycogen. Picroliv had no effect on the degree of parasitaemia.