Ferruginol Research Articles

Ferruginol and Sugiol: A Short Review of their Chemistry, Sources, Contents, Pharmacological Properties and Patents

In this short article, the chemistry, sources, contents, pharmacological properties and patents of ferruginol (FG) and sugiol (SG) are reviewed for the first time. Sources of information cited on these two abietane diterpenes were from databases such as Google, Google Scholar, PubMed, Science Direct, J-Stage, Web of Science and PubChem. In the selection of articles, recent references were accorded higher priority apart from their relevance to the topics. Both FG and SG are characterized by a tricyclic ring system with a hydroxyl group and an isopropyl group at ring C. SG has a carbonyl group at ring B that is absent in FG. Found in the bark and root of plant species particularly those belonging to the families Cupressaceae and Lamiaceae, FG and SG have attracted much attention because of their diverse pharmacological properties, notably, their anti cancer and anti-protozoal activities. Three patents on FG and one on SG are described. Some areas of research requiring further investigations are suggested.

Synergistic Effects of Ginsenoside Rb3 and Ferruginol in Ischemia-Induced Myocardial Infarction.

Previous research shows that ginsenoside Rb3 (G-Rb3) exhibit significant protective effects on cardiomyocytes and is considered a promising treatment for myocardial infraction (MI). However, how to improve its oral bioavailability and reduce its dosage remains to be studied. Previous studies suggest that Ferruginol (FGL) may have synergistic effects with G-Rb3. However, the underlying mechanisms remain to be explored. In this study, left anterior descending branch (LAD) coronary artery ligation or oxygen-glucose deprivation-reperfusion (OGD/R) were used to establish MI models in vivo and in vitro. Subsequently, the pharmacological effects and mechanisms of G-Rb3-FGL were explored by in vitro studies. The results showed that the G-Rb3-FGL co-treatment improved heart functions better than the G-Rb3 treatment alone in MI mice models. Meanwhile, the G-Rb3-FGL co-treatment can upregulate fatty acids oxidation (FAO) and suppress oxidative stress in the heart tissues of MI mice. In vitro studies demonstrated that the synergistic effect of G-Rb3-FGL on FAO, oxidation and inflammation was abolished by RXRα inhibitor HX531 in the H9C2 cell model. In summary, we revealed that G-Rb3 and FGL have a synergistic effect against MI. They protected cardiomyocytes by promoting FAO, inhibiting oxidative stress, and suppressing inflammation through the RXRα-Nrf2 signaling pathway.

Ferruginol Restores SIRT1-PGC-1α-Mediated Mitochondrial Biogenesis and Fatty Acid Oxidation for the Treatment of DOX-Induced Cardiotoxicity.

Background: Doxorubicin (DOX), a broad-spectrum chemotherapy drug, has life-threatening cardiotoxicity. Therefore, searching cardioprotective drugs for DOX-induced cardiotoxicity (DIC) is urgently needed. Objectives: This study aimed to explore cardioprotective effect and specific mechanism by which Ferruginol (FGL) attenuated DIC in vivo and in vitro. Methods: We evaluated the cardioprotection of FGL and performed high-throughput RNA-Seq on a DIC mouse. Whereafter, multiple methods, including western blot, RT-qPCR, a transmission electron microscope, CO-IP, immunofluorescence, and other staining methods, and antagonist of SIRT1 and PGC-1α were utilized to confirm the cardioprotection and molecular mechanism of FGL. Results: FGL-exerted cardioprotection manifested as enhanced cardiac function and reduced structural damage and apoptosis. The transcriptome and other results revealed that FGL facilitated PGC-1α-mediated mitochondrial biogenesis and fatty acid oxidation (MB and FAO) by increasing the expression of PGC-1α and concurrently promoting the expression of SIRT1-enhancing deacetylase SIRT1 deacetylating and activating PGC-1α. Conclusions: These results documented that FGL exerted cardioprotective effects restoring MB&FAO via the SIRT1–PGC-1α axis.

Ferruginol-induced apoptosis in Human Colon Cancer Cells (HCT-116) through the mitochondria-mediated apoptotic pathway

Background: Colon cancer is the third leading cause of cancer-related deaths globally. Despite advances in systemic therapies, colorectal cancer still remains one of the foremost challenges due to high mortality rate. Objectives: In this current investigation, we observed the anticancer and proapoptotic potentials of ferruginol (FGL) in human colon cancer (HCT-116) cells. Materials and Methods: We recognized that the potentials of FGL against cell viability in HCT-116 cells were determined by MTT assay. Production of reactive oxygen species (ROS), status of mitochondrial membrane potential (MMP), catalase (CAT), superoxide dismutase (SOD), diminished glutathione (GSH), and thiobarbituric acid-reactive substances (TBARS) were also evaluated. In addition, apoptotic protein expressions such as bax, caspase-9, cytochrome-c, Bcl-2, and caspase-3 were assessed through Western blotting analysis. Results: Our findings showed that FGL induced apoptosis as confirmed through the thrashing of cell viability, improved ROS formation and TBARS, and decreased antioxidants (SOD, CAT, and GSH) and MMP in HCT-116 cells. Further, the proapoptotic role of FGL was downregulated the Bcl-2 expression, whereas improved caspase-9, Bax, caspase-3, and cytochrome-c expressions in HCT-116 cells. Conclusion: Therefore, FGL stimulates apoptosis in HCT-116 cells through triggering oxidative damage and mitochondrial-mediated apoptotic pathway.

Ameliorative effect of ferruginol on isoprenaline hydrochloride‐induced myocardial infarction in rats

Cardiovascular-related diseases continue to be a leading cause of death globally. Among ischemic-induced cardiac diseases, myocardial infarction (MI) is reported to be of an alarming value. Despite numerous improvements in the medical intrusions, still this armamentarium fails to be effective in managing the illness without setbacks. Ferruginol (FGL) is a major polyphenols and terpenoids with numerous pharmacological activities including antioxidant and anti-inflammatory. Following, this work was aimed to explore the cardio protective effect of FGL (50 mg/kg) in isoprenaline hydrochloride (ISO)-induced MI in experimental rats. After treatment with FGL in ISO-induced MI in rats, noticeable changes were observed in the experimental rats. Injection of ISO to rats resulted in the augmented cardiac weight, serum cardiac markers (creatine kinase, creatine kinase-MB, cardiac troponin T, and Cardiac troponin I), lipid peroxidation end products (thiobarbituric acid-reactive substance and lipid hydroperoxides), reduced endogenous antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione), reduced ATPase activity, and escalated pro-inflammatory cytokines (interleukin-6, tumor necrosis factor-α, and nuclear factor-κB) levels. Interestingly, the FGL supplementation to the ISO-treated rats revealed the diminished heart weight, reduced cardiac markers, and lipid peroxidation. FGL also possessed the improved antioxidants status and diminished pro-inflammatory mediator levels. The outcomes of histological analysis also evidenced the cardio protective role of FGL. Treatment with FGL reduced the cardiac damage biomarkers maintained to near normal levels in ISO-induced rats. These study findings disclose the prospective capability of FGL in the treatment of MI in the future.

Pharmacokinetics and Tissue Distribution Study of Ferruginol in Wistar Rat by High-performance Liquid Chromatography

Background: Ferruginol (FRGN) exhibits a broad range of pharmacological properties which make it a promising candidate for chemoprevention. However, little is known about its absorption, distribution, metabolism, excretion, and toxicity (ADMET) properties. Methods: A rapid, sensitive and specific HPLC-DAD method was established to quantify FRGN in the plasma and tissues of Wistar rats. After extraction of FRGN with ethyl acetate (EtOAc), chromatographic separation was performed on a YMC ODS C18 column (250 × 4.6 mm I.D., 5 µm) with a mobile phase consisting of methanol-water (92:8, v/v) at a flow rate of 0.9 mL/min. Detection was conducted with a wavelength of 273 nm at 25 °C. Results: The calibration curves for FRGN were linear in the concentration range of 0.5-20 µg/mL for plasma, 0.5-10 µg/mL for heart, liver, spleen, lung, kidney, stomach, intestine, brain and muscle. After three cycles of freezing and thawing, the concentration variations were within ± 7% of nominal concentrations, indicating no significant substance loss during repeated thawing and freezing. The assay was applied to pharmacokinetic and tissue distribution study in rats. Results suggested that lung, heart, liver, spleen and kidney were the major distribution tissues of FRGN in rats, and FRGN could permeate the blood-brain barrier to distribute in the brain of rats. Conclusion: The information provided by this research is very useful for gaining knowledge of the pharmacokinetic process and tissue distribution of FRGN.

Ferruginol induced apoptosis on SK-Mel-28 human malignant melanoma cells mediated through P-p38 and NF-κB.

In the present investigation, the antitumor effect of ferruginol (FGL) in SK-Mel-28 human malignant melanoma cells was studied. To investigate the cytotoxic property of FGL, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay was used. Results revealed that prolonged treatment duration decreases the IC25, IC50, and IC75 concentrations of FGL. The cytotoxicity was further confirmed by lactate dehydrogenase assay. As evident from comet assay, FGL induces DNA damage in a dose-dependent manner. Annexin V and 7-ADD assays showed that FGL-induced DNA damage triggers apoptosis-mediated cell death as confirmed by caspase-3 activity assay. As seen through Western blotting, FGL increases phosphorylation of p38 and nuclear translocation of NF-κB. Further, it was observed that p38 phosphorylation is responsible for NF-κB translocation to the nucleus. Further, inhibition of p38 phosphorylation and translocation of NF-κB decrease caspase-3 activity. The above finding confirms that caspase-3 activation is mediated through P-p38 and nuclear translocation of NF-κB. The present findings indicate that FGL significantly suppresses the proliferation of SK-Mel-28 cells in a dose- and time-dependent manner through induction of apoptosis. Furthermore, FGL executes apoptosis through phosphorylation of key protein such as p38 and translocation of NF-κB into the nucleus.

448. The oxidation of 4-methylthymol, ferruginol, and totarol

448. The oxidation of 4-methylthymol, ferruginol, and totarol