Anti-inflammatory and anti-apoptotic effect of zingiberene on isoproterenol-induced myocardial infarction in experimental animals.

This study aimed to investigate the antihyperlipidemic and anti-inflammatory effect of zingiberene (ZBN) on isoproterenol-(ISO) induced myocardial infarction in rats. ZBN (10 mg/kg b.wt.) was orally administered to rats for 21 days and ISO (85 mg/kg b.wt.) was subcutaneously injected into the rats at 24 h intervals for the last 2 consecutive days. We observed increased serum creatine kinase, creatine kinase-MB, cardiac troponin T, and I levels in ISO-treated MI rats. Conversely, ZBN oral administration significantly prevented in cardiac marker enzyme activities in ISO-mediated rats. We also noticed that ZBN oral administration prevented ISO-induced expression of lipid peroxidative markers, total cholesterol, triglycerides, phospholipids, free fatty acids, very-low-density lipoprotein cholesterol (VLDL-C), low-density lipoprotein cholesterol (LDL-C) to the normal basal level. Furthermore, ZBN restored ISO-mediated antioxidant status, increased level of high-density lipoprotein cholesterol (HDL-C), and tissue phospholipids to the near-normal levels. Besides, ZBN pre-treatment significantly reduced the level of inflammatory markers (TNF-α, IL-6, NF-κB, and IL-1ß) in ISO-induced MI in rats. We noticed that ZBN pretreatment inhibited the pro-apoptotic proteins Bax and cytochrome c and increased the Bcl-2 expression in ISO induced rats. The gene expression profiling by qRT-PCR array illustrates that ZBN treatment prevents the ISO mediated activation of cardiac markers, inflammatory, and fibrosis-related genes in the heart tissue. Taken together, pre-treatment with ZBN attenuated ISO-induced MI resolved exhibits the anti-inflammatory and antiapoptotic effect.

Zingiberene targets the miR-16/cyclin-B1 axis to regulate the growth, migration and invasion of human liver cancer cells.

PURPOSE: Liver cancer or hepatocellular carcinoma (HCC) is considered as one of the most frequent malignancies with significantly high morbidity and mortality across the globe. MicroRNAs (miRs) are regarded as important regulators of liver cancer formation and its development. However, the full biochemical mechanism of their role is still very less understood. The main objective of the current research work was to examine the role of miR-16/cyclin-B1 axis in liver cancer regulation and how this pathway along with liver cancer migration and invasion are targeted by zingiberene molecule. METHODS: Quantitative reverse transcriptase polymerase chain reaction was used to evaluate miR-16 expression in HCC cell lines. Western blotting was performed to evaluate the expression of the miR-16 target genes. Effects on cell migration and invasion were evaluated by in vitro wound healing assay and transwell Matrigel assay, respectively. Effects of zingiberene on HCC cell viability were evaluated by MTT assay. RESULTS: Zingiberene treatment led to downregulation of miR-16 in HepG2 human hepatocellular carcinoma cells, accompanied by induction of G0/G1 cell cycle arrest targeting cyclin B1 as direct target. These effects were also accompanied by inhibition of cell migration and invasion, indicating that miR-16 can have a significant role as liver cancer suppressor after zingiberene treatment. Luciferase reporter assay confirmed that miR-16, which was one of HCC downregulated miRs, directly targeted Cyclin B1 in HCC cells. CONCLUSION: The current study indicates miR-16/cyclin B1 axis might have significant applications as a therapeutic target for patients with liver cancer.

α-Bisabolol suppresses the inflammatory response and ECM catabolism in advanced glycation end products-treated chondrocytes and attenuates murine osteoarthritis.

As a chronic musculoskeletal degeneration disease, osteoarthritis (OA) clinically manifests as joint pain, stiffness and a limited range of movement. OA has affected the life quality of at least one-tenth of the population but lacks satisfactory treatments. α-Bisabolol (BISA) is a small oily sesquiterpene alcohol widely found in essential oils of chamomile (Matricaria recutita), salvia and wood of Candeia and has multiple biological properties, particularly an anti-inflammatory effect. The purpose of this study is to assess the anti-inflammatory and chondroprotective effect of BISA in OA progression and explore its underlying mechanism. We isolated human chondrocytes and treated them with advanced glycation end products (AGEs) to imitate OA progression in vitro. BISA pretreatment suppressed the AGE-induced inflammatory reaction and extracellular matrix (ECM) degeneration by blocking nuclear factor kappa B (NF-κB), p38 and c-Jun N-terminal kinase (JNK) signaling. Moreover, a mouse destabilization of the medial meniscus (DMM) model was established by surgery to investigate BISA protection in vivo. BISA administration attenuated DMM-induced radiological and histopathological changes relative to the DMM group and resulted in lower OARSI scores. Taken together, the results of our study indicate the potential of BISA in OA therapy.

Anti-hyperalgesic effect of (-)-α-bisabolol and (-)-α-bisabolol/ß-Cyclodextrin complex in a chronic inflammatory pain model is associated with reduced reactive gliosis and cytokine modulation.

Chronic pain is a continuous or recurring pain which exceeds the normal course of recovery to an injury or disease. According to the origin of the chronic pain, it can be classified as inflammatory or neuropathic. This study aimed to evaluate the antinociceptive and anti-inflammatory effect of (-)-α-bisabolol (BIS) alone and complexed with ß-cyclodextrin (ßCD) in preclinical models of chronic pain. Chronic pain was induced by Freund's Complete Adjuvant (FCA) or partial lesion of the sciatic nerve (PLSN). Swiss mice were treated with BIS, BIS-ßCD (50 mg/kg, p.o) or vehicle (control) and mechanical hyperalgesia, thermal hyperalgesia, muscle strength and motor coordination were evaluated. In addition, levels of TNF-α and IL-10 and expression of the ionized calcium-binding adapter protein (IBA-1) were assessed in the spinal cord of the mice. The complexation efficiency of BIS in ßCD was evaluated by High-Performance Liquid Chromatography. BIS and BIS-ßCD reduced (p < 0.001) mechanical and thermal hyperalgesia. No alterations were found in force and motor coordination. In addition, BIS and BIS-ßCD inhibited (p < 0.05) TNF-α production in the spinal cord and stimulated (p < 0.05) the release of IL-10 in the spinal cord in PLSN-mice. Further, BIS and BIS-ßCD reduced IBA-1 immunostaining. Therefore, BIS and BIS-ßCD attenuated hyperalgesia, deregulated cytokine release and inhibited IBA-1 expression in the spinal cord in the PLSN model. Moreover, our results show that the complexation of BIS in ßCD reduced the therapeutic dose of BIS. We conclude that BIS is a promising molecule for the treatment of chronic pain.

Actividad in vitro anti-Leishmania (Trypanosomatidae) del epóxido trans-Z-&-bisaboleno y del Safrol, en frutos de Piper auritum (Piperaceae) / Anti-Leishmania (Trypanosomatidae) activity of trans-Z-&-bisabolene epoxide and isolation of safrole, in fruits of Piper auritum (Piperaceae)

Resumen La leishmaniasis es una enfermedad con una alta incidencia en el ser humano, que puede ser controlada, pero como los tratamientos tienen efectos secundarios importantes se han realizado estudios de diversas plantas con el fin de encontrar compuestos con actividad antileishmaniásica que presenten pocos efectos nocivos para el ser humano. El presente estudio consistió en realizar un tamizaje fitoquímico de la planta, para identificar la presencia de cumarinas, terpenos, triterpenos y azúcares reductores. El objetivo fue encontrar componentes químicos puros con actividad contra el parásito Leishmania sp. Por tal razón se purificaron los compuestos: trans-Z-alfabisaboleno y el Safrol, a los que se les realizaron pruebas del efecto anti parasitario que presentaron un CI50 de 50.0 µg/mL y 0.0 µg/mL, respectivamente. Además, se discute la importancia de estos nuevos hallazgos. El compuesto mayoritario presente en los aceites esenciales (Safrol) no es el componente que presentó la actividad. Es importante realizar estudios sobre su proyección en el tratamiento de la leishmaniasis.

Abstract The leishmaniosis disease incidence is high in tropical regions, and its current treatment has shown severe secondary effects. Considering this problem, many studies have focused on plants, looking for chemical components that have anti-leishmanial activity, and are free of adverse effects for human beings. The purpose of this work was to find a chemical component with this kind of activity in Piper auritum. In a phytochemical screening of this plant, we found some cumarins, terpens, triterpens and reducing sugars; and later, we identified the components trans-Z-α-bisabolene epoxide and Safrol. The first component presented a CI50 of 50.0 µg/mL of anti-Leishmania activity. The Safrol, which is the major component of the essential oils of this plant, did not show antiparasitic activity. These results are discussed considering treatment of leishmaniasis. Rev. Biol. Trop. 66(2): 826-835. Epub 2018 June 01.