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Objective: To explore how germacrone regulates the proliferation, migration and chemoresistance of human thyroid cancer BCPAP cells and doxorubicin (DOX) resistant BCPAP cells (BCPAP/DOX) through the forkhead box O3 (FOXO3)-FOX subclass M1 transcription factor (FOXM1) signaling pathway. Methods: BCPAP cells were cultured routinely and used to construct BCPAP/DOX cells. MTT method was applied to detect the effects of different concentrations of germacrone on the proliferation of BCPAP and BCPAP/DOX cells. BCPAP and BCPAP/DOX cells were divided into control group (Ctrl), negative control group (NC, transfected with sh-NC plasmid), low concentration germacrone group (0.10 mmol/L), high concentration germacrone group (0.15 mmol/L), high concentration germacrone (0.15 mmol/L) + sh-FOXO3 group (transfected with sh-FOXO3 plasmid). The sh-NC plasmid and sh-FOXO3 plasmid were transfected into the corresponding BCPAP and BCPAP/DOX cells with transfection reagents. The proliferation and migration of the cells were detected using CCK-8 assay and scratching healing assay, and the expression of FOXO3, FOXM1, BAX, MMP-9 and multi-drug resistant-1 (MDR-1) was detected using WB assay. Results: The expression of FOXO3 was successfully knocked down in BCPAP and BCPAP/DOX cells. Both low and high concentrations of germacrone could significantly inhibit the proliferation and migration of BCPAP and BCPAP/DOX cells, reduce the protein expression of FOMX1, MMP-9 or MDR-1 (in BCPAP/ DOX cells), and increase the protein expression of FOXO3 and BAX (all P < 0.05). Notably, the effects were more significant with high concentration germacrone compared to that of low concentration (all P < 0.05). Knockdown of FOXO3 partially reversed the effects of germacrone on these cells (all P < 0.05). Conclusion: Germacrone may regulate the proliferation and migration of BCPAP and BCPAP/DOX cells and reduce chemotherapy resistance of BCPAP/DOX cells through the FOXO3/FOXM1 signaling pathway. [ABSTRACT FROM AUTHOR]

Abnormal melanin synthesis causes hyperpigmentation disorders, such as chloasma, freckles, and melanoma, which are highly multiple and prevalent. There were few reports on the anti-melanogenic effect of Curcuma wenyujin Y.H. Chen et C. Ling, and the bioactive compound has not been elucidated as well. The study aims to investigate the anti-melanogenic effect of C. wenyujin, and identify the bioactive compound, and further explore its underlying mechanism. Our results showed that the Petroleum ether fraction extracted from C. wenyujin rhizome had a significant anti-melanogenic effect, and germacrone isolated from it was confirmed as the major bioactive compound. To our data, germacrone significantly inhibited tyrosinase (TYR) activity, reduced melanosome synthesis, reduced dendrites formation of B16F10 cells, and melanosome transport to keratinocytes. Moreover, germacrone effectively decreased the hyperpigmentation in zebrafish and the skin of guinea pigs in vivo. Western-blot analysis showed that germacrone down-regulated the expression of TYR, TRP-1, TRP-2, Rab27a, Cdc42, and MITF proteins via the activation of the MAPK signaling pathway. Taken together, germacrone is an effective bioactive compound for melanogenesis inhibition. Our studies suggest that germacrone may be considered a potential candidate for skin whitening. [ABSTRACT FROM AUTHOR]

Retinal ischemia-reperfusion (I/R) is a pathological phenomenon that causes cellular destruction in several ocular disorders, so there is a need for novel possible neuroprotective drugs. Researchers have reported numerous neuroprotective effects of Germacrone (GM). Therefore, this study aimed to elucidate the underlying processes of GM that may contribute to glaucoma development. 40 healthy rats underwent retinal ischemia-reperfusion (I/R) damage. The animals were divided into control, I/R-induced, GM-1d, and GM-7d. After 7 days of I/R, mice were sacrificed and retinal tissue removed. An enzyme-linked immunosorbent assay (ELISA) was used to assess retinal Malondialdehyde (MDA) and 8-OHdG levels after oxidative injury. The Fluro-Gold (FG) labelling assay counted retinal ganglion cells (RGC) before and after labelling. DNA from retinal tissue RNA was amplified. Western blotting and real-time qRT-PCR were utilised to assess Bax, Casapses-3, Bcl-2, retinal NF-kB, and COX-2 expression. Retinal cell apoptotic mediator expression was measured by a TUNEL assay. Retinal I/R damage increases ganglion cell death. Long-term GM treatment (GM-7d) reduced NF-κB activation and raised COX-2 expression, which suggests antioxidant potential. TUNEL-positive apoptotic cells were reduced in long-term GM-treated rats. In GM-treated retinas, the Bax-Bcl-2 ratio was identical to the control group and significantly different from the I/R group. GM reduces I/R-induced retinal cell damage by inhibiting RG cell death. Seven days after GM therapy, histology showed retinal tissue loss. NF-κB signaling and intrinsic mitochondrial apoptosis are possible mechanisms that may be attenuated by GM and are attributed to a retinal protective effect. [ABSTRACT FROM AUTHOR]

Bone is one of the most frequent sites for metastasis in breast cancer patients. Bone metastasis significantly reduces the survival time and the life quality of breast cancer patients. Germacrone (GM) can serve humans as an anti‐cancer and anti‐inflammation agent, but its effect on breast cancer‐induced osteolysis remains unclear. This study aims to investigate the functions and mechanisms of GM in alleviating breast cancer‐induced osteolysis. The effects of GM on osteoclast differentiation, bone resorption, F‐actin ring formation, and gene expression were examined in vitro. RNA‐sequencing and Western Blot were conducted to explore the regulatory mechanisms of GM on osteoclastogenesis. The effects of GM on breast cancer‐induced osteoclastogenesis, and breast cancer cell malignant behaviors were also evaluated. The in vivo efficacy of GM in the ovariectomy model and breast cancer bone metastasis model with micro‐CT and histomorphometry. GM inhibited osteoclastogenesis, bone resorption and F‐actin ring formation in vitro. Meanwhile, GM inhibited the expression of osteoclast‐related genes. RNA‐seq analysis and Western Blot confirmed that GM inhibited osteoclastogenesis via inhibition of MAPK/NF‐κB signaling pathways. The in vivo mouse osteoporosis model further confirmed that GM inhibited osteolysis. In addition, GM suppressed the capability of proliferation, migration, and invasion and promoted the apoptosis of MDA‐MB‐231 cells. Furthermore, GM could inhibit MDA‐MB‐231 cell‐induced osteoclastogenesis in vitro and alleviate breast cancer‐associated osteolysis in vivo human MDA‐MB‐231 breast cancer bone metastasis‐bearing mouse models. Our findings identify that GM can be a promising therapeutic agent for patients with breast cancer osteolytic bone metastasis. [ABSTRACT FROM AUTHOR]

Diabetic nephropathy (DN) is a severe complication of diabetes and the leading cause of end-stage renal disease and death. Germacrone (Ger) possesses anti-inflammatory, antioxidant and anti-DN properties. However, it is unclear whether the improvement in kidney damage caused by Ger in DN mice is related to abnormal compositions and metabolites of the gut microbiota. This study generates a mouse model of DN to explore the potent therapeutic ability and mechanism of Ger in renal function by 16S rRNA sequencing and untargeted fecal metabolomics. Although there is no significant change in microbiota diversity, the structure of the gut microbiota in the DN group is quite different. Serratia_marcescens and Lactobacillus_iners are elevated in the model group but significantly decreased after Ger intervention (P

The extraction and purification procedures, crystallization and crystal structure refinement (single-crystal X-ray data) of germacrone type II, C15H22O, are presented. The structural results are compared with a previous powder X-ray synchrotron study [Kaduk et al. (2022). Powder Diffr. 37, 98–104], revealing significant improvements in terms of accuracy and precision. Hirshfeld atom refinement (HAR), as well as Hirshfeld surface analysis, give insight into the intermolecular interactions of germacrone type II.

Malignant disease or cancer progression burden the community after decades. This tumor formation or tumorigenesis involves cell proliferation. Protein Kinases (MAPK9s) is key proteins of regulating the growth and viability of cells physiologically and pathologically. Rhizomes of Curcuma zedoaria or zedoary or white turmeric is used as a health supplement. The aim of this study was to obtained candidate proteins for anti-proliferative using the docking method between the protein MAPK9 and the active compound obtained from the crude extract of white turmeric i.e. demethoxycurcumin, curcumenol and germacrone. The result s hows that complex MAPK-demethoxycurcumin have the lowest binding affinity -8.4 Kkal/mol, while MAPK-curcumenol was -8 Kkal/mol, and MAPK-Germacrone was -6.2 Kkal/mol, it determined the potential activity cell proliferation.

Macrophages can transform into M1 (pro-inflammatory) and M2 (anti-inflammatory) phenotypes, which mediate the immune/inflammatory response in rheumatoid arthritis (RA). Activated M1 phenotype macrophages and overexpression of folate (FA) receptors are abundant in inflammatory synovium and joints and promote the progression of RA. Germacrone (GER) can regulate the T helper 1 cell (Th1)/the T helper 2 cell (Th2) balance to delay the progression of arthritis. To deliver GER to inflammatory tissue cells to reverse M1-type proinflammatory cells and reduce inflammation, FA receptor-targeting nanocarriers loaded with GER were developed. In activated macrophages, FA-NPs/DiD showed significantly higher uptake efficiency than NPs/DiD. In vitro experiments confirmed that FA-NPs/GER could promote the transformation of M1 macrophages into M2 macrophages. In adjuvant-induced arthritis (AIA) rats, the biodistribution profiles showed selective accumulation at the inflammatory site of FA-NPs/GER, and significantly reduced the swelling and inflammation infiltration of the rat's foot. The levels of pro-inflammatory cytokines (TNF-α, IL-1β) in the rat's inflammatory tissue were significantly lower than other treatment groups, which indicated a significant therapeutic effect in AIA rats. Taken together, macrophage-targeting nanocarriers loaded with GER are a safe and effective method for the treatment of RA.

Mitophagy is a critical intracellular event during the progression of diabetic nephropathy (DN). Our previous study demonstrated that germacrone has anti-ferroptotic properties and is a potential therapeutic agent for DN. However, the relationship among germacrone, mitophagy, and ferroptosis in DN remains unclear. In this study, the data confirmed that germacrone ameliorates high glucose (HG)-induced ferroptosis through limiting Fe (2þ) content and lipid reactive oxygen species (ROS) accumulation in human kidney 2 (HK-2) cells. Germacrone reversed HG-mediated inhibition of mitophagy. Mitophagy inhibition and anabatic mitochondrial ROS abrogate germacrone-mediated protective effects against ferroptotic death, resulting in the subsequent activation of mitochondrial DNA (mtDNA) cytosolic leakage-induced stimulator of interferon response CGAMP interactor 1 (STING) signaling. The combination of a mitochondrial ROS antagonist and germacrone acts synergistically to alleviate the ferroptotic death of tubular cells and DN symptoms. In summary, germacrone ameliorated ferroptotic death in tubular cells by reactivating mitophagy and inhibiting mtDNA-STING signaling in DN. This study provides a novel insight into germacrone-mediated protection against DN progression and further confirms that antioxidant pharmacological strategies facilitate the treatment of DN. [ABSTRACT FROM AUTHOR]

Germacrone and curdione are germacrane-type sesquiterpenoids that are widely distributed and have extensive pharmacological activities; they are the main constituents of 'Xing-Nao-Jing Injection' (XNJ). Studies on the metabolic features of germacrane-type sesquiterpenoids are limited. In this study, the metabolites of germacrone and curdione were characterized by UHPLC-Q-Exactive Oribitrap mass spectrometry after they were orally administered to rats. In total, 60 and 76 metabolites were found and preliminarily identified in rats administered germacrone and curdione, respectively, among which at least 123 potential new compounds were included. New metabolic reactions of germacrane-type sesquiterpenoids were identified, which included oxidation (+4 O and +5 O), ethylation, methyl-sulfinylation, vitamin C conjugation, and cysteine conjugation reactions. Among the 136 metabolites (including 113 oxidation metabolites, two glucuronidation, two methylation, nine methyl-sulfinylation, three ethylation, six cysteine conjugation, and one Vitamin C conjugation metabolites), 32 metabolites were detected in nine organs, and the stomach, intestine, liver, kidneys, and small intestine were the main organs for the distribution of these metabolites. All 136 metabolites were detected in urine and 64 of them were found in feces. The results of this study not only contribute to research on in vivo processes related to germacrane-type sesquiterpenoids but also provide a strong foundation for a better understanding of in vivo processes and the effective forms of germacrone, curdione, and XNJ. [Display omitted] • Distribution of the metabolites of germacrane-type sesquiterpenes were studied. • ESI MS fragmentation rules of germacrane-type sesquiterpenes were summarized. • 60 and 76 metabolites of germacrone and curdione were identified in rats. • Among 136 metabolites, 123 were potential new compounds. • 5 metabolic reactions of germacrane-type sesquiterpenes were discovered in rats. [ABSTRACT FROM AUTHOR]

Curcumin and germacrone, natural products present in the Zingiberaceae family of plants, have several biological properties. Among these properties, the anti-NSCLC cancer action is noteworthy. In this paper, kinetics of the two compounds in rat liver microsomes (RLMs), human liver microsomes (HLMs), and cytochrome P450 (CYP) enzymes (CYP3A4, 1A2, 2E1, and 2C19) in an NADPH-generating system in vitro were evaluated by UP-HPLC–MS/MS (ultrahigh-pressure liquid chromatography–tandem mass spectrometry). The contents of four cytochrome P450 (CYP) enzymes, adjusting by the compounds were detected using Western blotting in vitro and in vivo. The t1/2 of curcumin was 22.35 min in RLMs and 173.28 min in HLMs, while 18.02 and 16.37 min were gained for germacrone. The Vmax of curcumin in RLMs was about 4-fold in HLMs, meanwhile, the Vmax of germacrone in RLMs was similar to that of HLMs. The single enzyme t1/2 of curcumin was 38.51 min in CYP3A4, 301.4 min in 1A2, 69.31 min in 2E1, 63.01 min in 2C19; besides, as to the same enzymes, t1/2 of germacrone was 36.48 min, 86.64 min, 69.31 min, and 57.76 min. The dynamic curves were obtained by reasonable experimental design and the metabolism of curcumin and germacrone were selected in RLMs/HLMs. The selectivities in the two liver microsomes differed in degradation performance. These results meant that we should pay more attention to drugs in clinical medication–drug and drug–enzyme interactions. [ABSTRACT FROM AUTHOR]

The crystal structure of a new polymorph of germacrone has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional theory techniques. This polymorph (Form II) crystallizes in space group C2/c (#15) with a = 26.0073(4), b = 9.84383(10), c = 10.53713(13) Å, β = 95.7547(11)°, V = 2684.04(3) Å3, and Z = 8. The crystal structure is dominated by van der Waals interactions, but four C–H⋯O hydrogen bonds are present. The structure exhibits many similarities to the previously reported Form I polymorph FIQLOG, but is clearly different. The powder pattern has been submitted to ICDD for inclusion in the Powder Diffraction File™ (PDF). [ABSTRACT FROM AUTHOR]

Abstract Background Germacrone (GM) is a terpenoid compound which is reported to have anti-inflammatory and anti-oxidative effects. However, its role in treating traumatic brain injury (TBI) remains largely unknown. Methods Male C57BL/6 mice were divided into the following groups: control group, TBI group [controlled cortical impact (CCI) model], CCI + 5 mg/kg GM group, CCI + 10 mg/kg GM group and CCI + 20 mg/kg GM group. GM was administered via intraperitoneal injection. The neurological functions (including motor coordination, spatial learning and memory abilities) and brain edema were measured. Nissl staining was used to detect the neuronal apoptosis. Colorimetric assays and enzyme linked immunosorbent assay (ELISA) kits were used to determine the expression levels of oxidative stress markers including myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of inflammatory markers, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Additionally, protein levels of Nrf2 and p-p65 were detected by Western blot assay. Results GM significantly ameliorated motor dysfunction, spatial learning and memory deficits of the mice induced by TBI and it also reduced neuronal apoptosis and microglial activation in a dose-dependent manner. Besides, GM treatment reduced neuroinflammation and oxidative stress compared to those in the CCI group in a dose-dependent manner. Furthermore, GM up-regulated the expression of antioxidant protein Nrf2 and inhibited the expression of inflammatory response protein p-p65. Conclusions GM is a promising drug to improve the functional recovery after TBI via repressing neuroinflammation and oxidative stress.

Aims: Diabetic nephropathy (DN) is characterized by microalbuminuria, mainly associated with pathological and morphological alterations of podocyte. New drug targeting podocyte injury is a promising approach for treating DN. The present study is aimed at developing new drug targeting podocyte injury for treating DN. Results: In this study, germacrone ameliorated kidney damage and inhibited podocyte apoptosis in a DN mouse model. Based on RNA-seq, mmu_mmu_circRNA_0000309, located in host gene vascular endothelial zinc finger 1 (Vezf1), showed a sharp decline in DN mice and a remarkable recovery in germacrone-challenged DN mice. mmu_circRNA_0000309 silence or miR-188-3p mimics abrogated the antiapoptosis and anti-injury effects of germacrone through aggravating mitochondria damage, and elevating reactive oxygen species and ferroptosis-related protein levels. Mechanistically, mmu_circRNA_0000309 competitively sponged miR-188-3p, and subsequently promoted glutathione peroxidase 4 (GPX4) expression, thereby inactivating ferroptosis-dependent mitochondrial damage and podocyte apoptosis. In addition, GPX4 overexpression neutralized mmu_circRNA_0000309 silence-mediated mitochondria damage and ferroptosis in germacrone-exposed MPC5 cells. Innovation: We describe the novel effect and mechanism of germacrone on treating DN, which is linked to ferroptosis for the first time. Conclusion: mmu_circRNA_0000309 silence mediates drug resistance to germacrone in DN mice. mmu_circRNA_0000309 sponges miR-188-3p, and subsequently upregulates GPX4 expression, inactivating ferroptosis-dependent mitochondrial function and podocyte apoptosis. Possibly germacrone-based treatment for DN can be further motivated by regulating mmu_circRNA_0000309/miR-188-3p/GPX4 signaling axis. Antioxid. Redox Signal. 36, 740–759. [ABSTRACT FROM AUTHOR]

Abstract Hepatic stellate cells (HSCs) were activated and secreted excessive amounts of extracellular matrix (ECM) proteins during pathogenetic progress of liver fibrosis. Germacrone (GMO) and miR-29b can play an important role in inhibiting growth of HSCs and production of type I collagen. GMO and miR-29b were co-encapsulated into nanoparticles (NPs) based on poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA). Then, NPs were modified with cyclic RGD peptides (cRGDfK). cRGDfK is an effective ligand to bind integrin αvβ3 and increase the targeting ability for fibrotic liver. GMO- and miR-29b-loaded NPs exhibited great cytotoxicity to activated HSCs and significantly inhibited production of type I collagen. Liver fibrosis model of mice was induced by administration of carbon tetrachloride. Great targeting ability was achieved in liver fibrotic mice treated with cRGD-modified NPs. Significant ant-fibrotic effects have been presented based on hematoxylin and eosin (H&E), Masson and Sirius Red staining results of liver tissues collected from mice treated with drug-loaded NPs. All these results indicate GMO- and miR-29b-loaded cRGD-modified NPs have the potential for clinical use to treat liver fibrosis.

Ziqiang Yu, Jiuping Xu, Mingfeng Shao, Jianan Zou Department of Urology, The First Affiliated Hospital of Anhui University of Chinese Medicine, Hefei City, Anhui Province 230031, People’s Republic of ChinaCorrespondence: Mingfeng Shao; Jianan Zou Tel +86 55162850073Email sssmmmfff@126.com; zjamnwk@163.comBackground: Germacrone, a natural product isolated from the traditional Chinese medicine Rhizoma Curcuma, has been reported to exhibit antitumor activities in vitro. To further understand the antitumor mechanism of germacrone, we investigated the growth inhibitory effect of germacrone on the human prostate cancer cell lines PC-3 (androgen independent) and 22RV1 (androgen dependent).Materials and Methods: Prostate cancer cells were cultured with different concentrations of germacrone, and cell viability was measured by MTT assay. The levels of proteins were measured by Western blotting. Cell apoptosis was assessed by flow cytometry. Images of autophagy-related protein staining were captured by fluorescence microscopy. Autophagic flux was assessed by detecting the LC3B-II level.Results: Our results indicated that germacrone treatment significantly inhibited cell proliferation by inducing apoptosis in a dose-dependent manner, with IC50 values of 259 μM for PC-3 cells and 396.9 μM for 22RV1 cells. Germacrone-treated cells also exhibited induction of autophagy, as evidenced by elevated LC3B-II protein expression levels and punctuate patterns. Additionally, an autophagy inhibitor enhanced the growth inhibitory effect of germacrone. Moreover, the phosphorylation of Akt and mTOR was inhibited in germacrone-treated prostate cancer cells.Conclusion: Germacrone induced apoptosis and autophagy in prostate cancer cells by inhibiting the Akt/mTOR signaling pathway. Germacrone treatment also led to the activation of protective autophagy. These findings suggest that germacrone may potentially contribute to the development of a new therapeutic agent for prostate cancer treatment.Keywords: germacrone, prostate cancer cells, apoptosis, autophagy, Akt/mTOR

Abstract Background Germacrone is an anti-inflammatory ingredient in the Chinese medicine zedoary turmeric. The purpose of this study was to explore the protective mechanism of germacrone against PC12 cells injury caused by oxygen-glucose deprivation/reperfusion (OGD/R). Methods OGD/R injury model of PC12 cells was established by using OGD/R (2 h/24 h). The cell viability was assessed by MTT assay and LDH release. The ultrastructure of cells was observed by transmission electron microscopy (TEM). The expression of autophagy related proteins in cells was determined by Western Blot. Results The results of ultrastructural observation showed that PC12 cells damaged by OGD/R showed typical autophagy characteristics. In addition, OGD/R observably up-regulated the expression of autophagy related proteins: the class III type phosphoinositide 3-kinase (PI3K III), light chain 3(LC3), and Beclin-1 in PC12 cells, and inhibited the expression of the class I type phosphoinositide 3-kinase (PI3K I), Protein kinase B (Akt), the mammalian target of rapamycin (mTOR), and B-cell lymphoma 2(Bcl-2) proteins. Furthermore, germacrone increased the cell viability of OGD/R-damaged PC12 cells by down-regulating the expression of LC3 protein in cells in a concentration-dependent manner. More importantly, germacrone significantly inhibited the expression of PI3K III, LC3, and Beclin-1 in OGD/R-injured PC12 cells, and up-regulated the expressionof PI3K I, Akt, mTOR, and Bcl-2 proteins in cells, and this inhibited or up-regulated effect was reversed by PI3K I inhibitor (ZSTK474). Conclusion The above results indicated that germacrone could inhibit the autophagy effect in OGD/R injury model of PC12 cells, the mechanism of inhibition was regulated by PI3K III/Beclin-1/Bcl-2 and PI3K I/Akt/mTOR pathways, thereby improving the cell viability of PC12 cells and playing a neuroprotective role, which provided a new drug for the treatment of OGD/R.

Intestinal ischemia-reperfusion (I/R) injury severely affects the lungs. Germacrone (Ger) possesses anti-inflammatory and antioxidant properties. However, it is unclear whether it protects the lungs from I/R injury. In this study, we elucidate the mechanisms by which Ger protects lungs from I/R injury. C57BLKS/J male mice are subjected to I/R injury via complete clamping of the superior mesenteric artery. Ger is administered before intestinal I/R. Mitochondrial morphology is observed via electron microscopy. The histopathology of the lung tissues is monitored via hematoxylin-eosin and immunofluorescence staining. The mitochondrial oxygen consumption rate is measured via an XF96 extracellular flux analyzer. In the I/R mouse model, lung specimens present significant lung damage accompanied by increases in the levels of collagen III, vimentin, and α-SMA in lung tissues. After treatment with Ger, lung impairment and fibrosis in I/R-induced acute lung injury (ALI) model mice are restored, suggesting that Ger improves I/R-ALI. In addition, Ger administration decreases the release of inflammatory factors such as IL-1β, IL-6, and COX2, as well as the expressions of M1 macrophage markers, facilitating cell survival in the I/R-ALI model. Additionally, Ger (EC50: 47.16 μM) ameliorates mitochondrial dysfunction by increasing I/R-ALI-induced apoptosis, increasing the expression of SIRT1, and reducing the levels of HIF1-α, Nrf2, and OGG1 in MLE-12 cells. Ger may affect macrophage polarization and improve subsequent mitochondrial defects through the SIRT1-HIF1α-Nrf2 signaling pathway in MLE-12 cells, which ultimately improves lung function and lung inflammation in the I/R-ALI model.

Retinal ischemia-reperfusion (I/R) is a pathological phenomenon that causes cellular destruction in several ocular disorders, so there is a need for novel possible neuroprotective drugs. Researchers have reported numerous neuroprotective effects of Germacrone (GM). Therefore, this study aimed to elucidate the underlying processes of GM that may contribute to glaucoma development. 40 healthy rats underwent retinal ischemia-reperfusion (I/R) damage. The animals were divided into control, I/R-induced, GM-1d, and GM-7d. After 7 days of I/R, mice were sacrificed and retinal tissue removed. An enzyme-linked immunosorbent assay (ELISA) was used to assess retinal Malondialdehyde (MDA) and 8-OHdG levels after oxidative injury. The Fluro-Gold (FG) labelling assay counted retinal ganglion cells (RGC) before and after labelling. DNA from retinal tissue RNA was amplified. Western blotting and real-time qRT-PCR were utilised to assess Bax, Casapses-3, Bcl-2, retinal NF-kB, and COX-2 expression. Retinal cell apoptotic mediator expression was measured by a TUNEL assay. Retinal I/R damage increases ganglion cell death. Long-term GM treatment (GM-7d) reduced NF-κB activation and raised COX-2 expression, which suggests antioxidant potential. TUNEL-positive apoptotic cells were reduced in long-term GM-treated rats. In GM-treated retinas, the Bax-Bcl-2 ratio was identical to the control group and significantly different from the I/R group. GM reduces I/R-induced retinal cell damage by inhibiting RG cell death. Seven days after GM therapy, histology showed retinal tissue loss. NF-κB signaling and intrinsic mitochondrial apoptosis are possible mechanisms that may be attenuated by GM and are attributed to a retinal protective effect.

Abstract The extensive marine biodiversity has proved to be a promising source of substances with biomedical potential. In this study, the cytotoxicity of the Brazilian octocoral Phyllogorgia dilatata (Gorgoniidae) was evaluated against two tumor cell lines and three bacterial strains. The methanol/dichloromethane crude extract presented no antibacterial activity up to the highest concentration tested (512 µg/mL), however it revealed a noteworthy antiproliferative effect against HCT-116 (80%) and MCF-7 (54%) cell lines at 50 μg/mL. Therefore, guided by the cytotoxic activity, a multistep chemical fractionation of the extract provided the subfraction 5 (PDPH2-5) with IC50 values of 3.18 and 17.80 μg/mL against HCT-116 and MCF-7, respectively. The LC-HRMS/MS analysis of PDPH2-5 showed ions of m/z 219.1742 and 219.1743, characterized as (E,E) and (Z,E) germacrone, after a LC-DAD-SPE/NMR analysis of the hexanic fraction and comparisons of NMR data with the literature. Previously reported assessments to the cytotoxic activity of the (E,E)-diastereoisomer disclosed higher IC50 values than that obtained for the PDPH2-5 fraction, suggesting, herein, a potentiated effect of the diastereoisomeric mixture. Such remark encourage further bioactivity studies with stereoisomer mixtures and reduce the urge for compound isolation.

Liver fibrosis is an abnormal proliferation of connective tissue in the liver caused by various pathogenic factors. Chronic liver injury leads to release of inflammatory cytokines and reactive oxygen species (ROS) from damaged hepatocytes, which activates hepatic stellate cells (HSCs) to secrete extracellular matrix proteins, thereby leading to fibrosis. Thus, inhibition of hepatocyte injury and HSC activation, and promotion of apoptosis of activated HSCs are important strategies for prevention of liver fibrosis. In this study, we showed that the germacrone (GER), the main component in the volatile oil of zedoary turmeric, inhibited hepatic fibrosis by regulating multiple signaling pathways. First, GER improved the cell survival rate by inhibiting the production of ROS after hepatocyte injury caused by acetaminophen (APAP). In addition, GER inhibited the activation of HSCs and expression of collagen I by blocking TGF-β/Smad pathway in LX-2 cells. However, when the concentration of GER was higher than 60 μM, it specifically induced HSCs apoptosis by promoting the expression and activation of apoptosis-related proteins, but it had no effect on hepatocytes. Importantly, GER significantly attenuated the methionine- and choline-deficient (MCD) diet-induced liver fibrosis by inhibiting liver injury and the activation of HSCs in vivo. In summary, GER can not only protect hepatocytes by reducing ROS release to avoid the liver injury-induced HSC activation, but also directly inhibit the activation and survival of HSCs by regulating TGF-β/Smad and apoptosis pathways. These results demonstrate that GER can be used as a potential therapeutic drug for the treatment of liver fibrosis.

Liver fibrosis is an abnormal proliferation of connective tissue in the liver caused by various pathogenic factors. Chronic liver injury leads to release of inflammatory cytokines and reactive oxygen species (ROS) from damaged hepatocytes, which activates hepatic stellate cells (HSCs) to secrete extracellular matrix proteins, thereby leading to fibrosis. Thus, inhibition of hepatocyte injury and HSC activation, and promotion of apoptosis of activated HSCs are important strategies for prevention of liver fibrosis. In this study, we showed that the germacrone (GER), the main component in the volatile oil of zedoary turmeric, inhibited hepatic fibrosis by regulating multiple signaling pathways. First, GER improved the cell survival rate by inhibiting the production of ROS after hepatocyte injury caused by acetaminophen (APAP). In addition, GER inhibited the activation of HSCs and expression of collagen I by blocking TGF-β/Smad pathway in LX-2 cells. However, when the concentration of GER was higher than 60 μM, it specifically induced HSCs apoptosis by promoting the expression and activation of apoptosis-related proteins, but it had no effect on hepatocytes. Importantly, GER significantly attenuated the methionine- and choline-deficient (MCD) diet-induced liver fibrosis by inhibiting liver injury and the activation of HSCs in vivo. In summary, GER can not only protect hepatocytes by reducing ROS release to avoid the liver injury-induced HSC activation, but also directly inhibit the activation and survival of HSCs by regulating TGF-β/Smad and apoptosis pathways. These results demonstrate that GER can be used as a potential therapeutic drug for the treatment of liver fibrosis. [ABSTRACT FROM AUTHOR]

Liver fibrosis is a primary threat to public health, owing to limited therapeutic options. Germacrone (GM) has been shown to exert various curative effects against human diseases, including liver injury. The aim of this study was to investigate the pharmacological effects of GM in the pathophysiology of hepatic fibrosis and determine its potential mechanisms of action. A liver fibrosis rat model was established via carbon tetrachloride (CCl4) treatment, and LX‐2 cells were stimulated with TGF‐β1. The effects of GM on liver fibrosis and its relationship with the phosphatidylinositol 3‐kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signalling pathway were investigated. In the CCl4 fibrosis‐induced rat model, GM improved histological damage, inhibited the activity of hepatic α‐smooth muscle actin and improved serum alanine aminotransferase and aspartate aminotransferase levels in a dose‐dependent manner. GM potently inhibited hepatic stellate cells (HSCs) growth and epithelial–mesenchymal transition (EMT) progression, as reflected by the altered expression of proliferative (Ki‐67, PCNA and cleaved caspase‐3) and EMT‐related (E‐cadherin and vimentin) proteins. In TGF‐β1‐stimulated LX‐2 cells, GM significantly inhibited the survival and activation of HSCs and induced cell apoptosis. GM also suppressed the migration ability and reversed the EMT process in HSCs. Following GM treatment, the phosphorylation of the PI3K, AKT and mTOR proteins was reduced in the liver of CCl4‐treated rats and TGF‐β1‐stimulated LX‐2 cells, indicating that GM may attenuate hepatic fibrosis via the PI3K/AKT/mTOR signalling pathway. These outcomes highlight the anti‐fibrotic effects of GM and suggest that it is a potential therapeutic agent for the treatment of liver fibrosis. Highlight: •Liver fibrosis is an important pathological feature in the early stages of liver disease.•Germacrone (GM) could potently inhibit hepatic stellate cell (HSC) growth, activation, and migration during the development of liver fibrosis. Mechanistically, GM may regulate HSC proliferation and activation, and epithelial–mesenchymal transition during liver fibrosis by targeting the phosphatidylinositol 3‐kinase/protein kinase B/mammalian target of rapamycin pathway. [ABSTRACT FROM AUTHOR]

Abstract Background Germacrone is one of the natural bioactive compounds found in Rhizoma curcuma essential oils. In this study, the potential anti-cancer effect of germacrone in gastric cancer cell line BGC823 was investigated. Methods The cell viability and proliferative activity were assessed, and cell cycle analysis was also performed. Hoechst 33258 and Annexin V/PI double staining was used for detection of cell apoptosis. Protein profiles of cell cycle-related and apoptosis-related proteins were assessed. Results MTT assay revealed that germacrone had marked cytotoxicity on BGC823 cells. Germacrone induced cell cycle arrest in the G2/M phase via remarkably decreased expression levels of cyclin B1, cdc 2 and cdc 25c. In addition, the treatment with germacrone induced caspase-3 activity and PARP cleavage. These findings demonstrated the effects of germacrone on inhibiting cell proliferation through induction of G2/M phase cell cycle arrest and promotion of cell apoptosis. It also indicated that germacrone functioned through modulations of cell cycle-associated protein expression and mitochondria-mediated apoptosis. Conclusion These findings will be valuable as the molecular basis for the germacrone-mediated anti-cancer effect against gastric cancer.

Curcuma xanthorrhiza Roxb. (Zingiberaceae) is a herbaceous perennial plant valued for its use in the pharmaceutical and food industry. In spite of its multipurpose use, the chemical composition of the leaf essential oil of the species is not known till date. Thus, the current work was undertaken to study the phytochemical composition and antioxidant activity of leaf essential oil of C. xanthorrhiza. GC/MS analysis of the leaf essential oil revealed the presence of 53 constituents; the major constituents being germacrone (18.76 %), xanthorrhizol (12.22 %), germacrene B (7.19 %), eucalyptol (6.89 %), γ-eudesmol acetate (6.33 %), ar-curcumene (6.06 %), β-himachalene (5.75 %) and curzerene (5.24 %). The essential oil was sesquiterpenoid in nature, with sesquiterpenes comprising 76.4 % of the oil. It consisted of 50.04 % oxygenated sesquiterpenes, 26.36 % sesquiterpene hydrocarbons, 10.31 % oxygenated monoterpenoids, 5.92 % aromatics, and 4.33 % monoterpene hydrocarbons. The DPPH and ABTS assay showed moderate antioxidant activity with IC50 value- 55.57±0.02 μg/mL and 24.42 μg/mL, respectively. To the best of our knowledge, this is the first report on the phytochemical composition and antioxidant activity of leaf essential oil of C. xanthorrhiza and this finding might be useful in undertaking advanced research on natural products. [ABSTRACT FROM AUTHOR]

In this work, we investigated the bioactivities of the essential oil (EO) extracted from the Rhododendron thymifolium and its principal germacrone against Lasioderma serricorne and Tribolium castaneum. The EO was obtained by steam distillation. Germacrone was obtained by cryogenic crystallization. The bioactivity of EO and germacrone was tested via contact and repellent activity assays. The results showed that EO and germacrone possessed contact and repellent activities against two species of insects. EO exhibited obvious contact activity against the L. serricorn adults, larvae and T. castaneum larvae with LD50 values of 29.15 µg/adult, 42.73 µg/larva, 19.65 µg/larva respectively. Germacrone exhibited excellent contact activity against the L. serricorne adults, larvae and the T. castaneum larvae with LD50 values of 17.18 µg/adult, 20.94 µg/larva, 20.93 µg/larva respectively. And at the highest testing concentrations (78.63 and 15.73 nL/cm2), the repellent activity of EO and germacrone on two target insects was comparable to that of the positive control (DEET) after 30 h exposure. In especially, in the treatment of the 120 h after the repellent activity of EO and germacrone against T.castaneum adults and larvae were still very significant and showed the same level percentage repellency as DEET. Meanwhile, germacrone exhibited inhibition of acetylcholinesterase activity with IC50 values of 3%. The results indicated that the EO of R. thymifolium and germacrone had the potential to be developed as natural insecticides and repellents for the control of T. castaneum and L. serricorne. [ABSTRACT FROM AUTHOR]

Germacrone, a monocyclic sesquiterpene, exerts marked antitumor effects in a variety of cancers, including hepatocellular carcinoma, gastric cancer, and breast cancer. However, the mechanism underlying the effects of germacrone on gastric cancer remains unclear. In this study, we show that germacrone inhibited gastric cancer cell proliferation in a dose-dependent manner, and induced G0/G1-phase cell cycle arrest and apoptosis in these cells. Moreover, germacrone increased the expression of LC3II/LC3I. And LC3II/LC3I was significant increased after germacrone treatment compared with germacrone and bafilomycin A1 (Baf A1) treatment, which suggested germacrone promoted the formation of autophagosomes. Proteomic analysis was then used to identify molecular targets of germacrone in gastric cancer. A total of 596 proteins were screened, and the top hit was identified as late endosomal/lysosomal adaptor and MAPK and MTOR activator 5 (LAMTOR5, also named HBXIP). Overexpression of HBXIP delayed the germacrone-induced cell cycle arrest, induction of apoptosis, and inhibition of autophagy. Combined, our results indicate that germacrone suppresses gastric cancer cell proliferation by inhibiting HBXIP, and this process is related to G0/G1-phase arrest and apoptosis.

Background: Germacrone (GM) is a terpenoid compound which is reported to have anti-inflammatory and anti-oxidative effects. However, its role in treating traumatic brain injury (TBI) remains largely unknown. Methods: Male C57BL/6 mice were divided into the following groups: control group, TBI group [controlled cortical impact (CCI) model], CCI + 5 mg/kg GM group, CCI + 10 mg/kg GM group and CCI + 20 mg/kg GM group. GM was administered via intraperitoneal injection. The neurological functions (including motor coordination, spatial learning and memory abilities) and brain edema were measured. Nissl staining was used to detect the neuronal apoptosis. Colorimetric assays and enzyme linked immunosorbent assay (ELISA) kits were used to determine the expression levels of oxidative stress markers including myeloperoxidase (MPO), malondialdehyde (MDA) and superoxide dismutase (SOD), as well as the expressions of inflammatory markers, including tumor necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). Additionally, protein levels of Nrf2 and p-p65 were detected by Western blot assay. Results: GM significantly ameliorated motor dysfunction, spatial learning and memory deficits of the mice induced by TBI and it also reduced neuronal apoptosis and microglial activation in a dose-dependent manner. Besides, GM treatment reduced neuroinflammation and oxidative stress compared to those in the CCI group in a dose-dependent manner. Furthermore, GM up-regulated the expression of antioxidant protein Nrf2 and inhibited the expression of inflammatory response protein p-p65. Conclusions: GM is a promising drug to improve the functional recovery after TBI via repressing neuroinflammation and oxidative stress. [ABSTRACT FROM AUTHOR]

Background: Germacrone is an anti-inflammatory ingredient in the Chinese medicine zedoary turmeric. The purpose of this study was to explore the protective mechanism of germacrone against PC12 cells injury caused by oxygen-glucose deprivation/reperfusion (OGD/R). Methods: OGD/R injury model of PC12 cells was established by using OGD/R (2 h/24 h). The cell viability was assessed by MTT assay and LDH release. The ultrastructure of cells was observed by transmission electron microscopy (TEM). The expression of autophagy related proteins in cells was determined by Western Blot. Results: The results of ultrastructural observation showed that PC12 cells damaged by OGD/R showed typical autophagy characteristics. In addition, OGD/R observably up-regulated the expression of autophagy related proteins: the class III type phosphoinositide 3-kinase (PI3K III), light chain 3(LC3), and Beclin-1 in PC12 cells, and inhibited the expression of the class I type phosphoinositide 3-kinase (PI3K I), Protein kinase B (Akt), the mammalian target of rapamycin (mTOR), and B-cell lymphoma 2(Bcl-2) proteins. Furthermore, germacrone increased the cell viability of OGD/R-damaged PC12 cells by down-regulating the expression of LC3 protein in cells in a concentration-dependent manner. More importantly, germacrone significantly inhibited the expression of PI3K III, LC3, and Beclin-1 in OGD/R-injured PC12 cells, and up-regulated the expressionof PI3K I, Akt, mTOR, and Bcl-2 proteins in cells, and this inhibited or up-regulated effect was reversed by PI3K I inhibitor (ZSTK474). Conclusion: The above results indicated that germacrone could inhibit the autophagy effect in OGD/R injury model of PC12 cells, the mechanism of inhibition was regulated by PI3K III/Beclin-1/Bcl-2 and PI3K I/Akt/mTOR pathways, thereby improving the cell viability of PC12 cells and playing a neuroprotective role, which provided a new drug for the treatment of OGD/R. [ABSTRACT FROM AUTHOR]

Background: Germacrone is one of the natural bioactive compounds found in Rhizoma curcuma essential oils. In this study, the potential anti-cancer effect of germacrone in gastric cancer cell line BGC823 was investigated. Methods: The cell viability and proliferative activity were assessed, and cell cycle analysis was also performed. Hoechst 33258 and Annexin V/PI double staining was used for detection of cell apoptosis. Protein profiles of cell cycle-related and apoptosis-related proteins were assessed. Results: MTT assay revealed that germacrone had marked cytotoxicity on BGC823 cells. Germacrone induced cell cycle arrest in the G2/M phase via remarkably decreased expression levels of cyclin B1, cdc 2 and cdc 25c. In addition, the treatment with germacrone induced caspase-3 activity and PARP cleavage. These findings demonstrated the effects of germacrone on inhibiting cell proliferation through induction of G2/M phase cell cycle arrest and promotion of cell apoptosis. It also indicated that germacrone functioned through modulations of cell cycle-associated protein expression and mitochondria-mediated apoptosis. Conclusion: These findings will be valuable as the molecular basis for the germacrone-mediated anti-cancer effect against gastric cancer. [ABSTRACT FROM AUTHOR]

Germacrone, a monocyclic sesquiterpene, exerts marked antitumor effects in a variety of cancers, including hepatocellular carcinoma, gastric cancer, and breast cancer. However, the mechanism underlying the effects of germacrone on gastric cancer remains unclear. In this study, we show that germacrone inhibited gastric cancer cell proliferation in a dose-dependent manner, and induced G0/G1-phase cell cycle arrest and apoptosis in these cells. Moreover, germacrone increased the expression of LC3II/LC3I. And LC3II/LC3I was significant increased after germacrone treatment compared with germacrone and bafilomycin A1 (Baf A1) treatment, which suggested germacrone promoted the formation of autophagosomes. Proteomic analysis was then used to identify molecular targets of germacrone in gastric cancer. A total of 596 proteins were screened, and the top hit was identified as late endosomal/lysosomal adaptor and MAPK and MTOR activator 5 (LAMTOR5, also named HBXIP). Overexpression of HBXIP delayed the germacrone-induced cell cycle arrest, induction of apoptosis, and inhibition of autophagy. Combined, our results indicate that germacrone suppresses gastric cancer cell proliferation by inhibiting HBXIP, and this process is related to G0/G1-phase arrest and apoptosis. [ABSTRACT FROM AUTHOR]

Copyright of Practical Pharmacy & Clinical Remedies is the property of Editorial Department of Practical Pharmacy & Clinical Remedies and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Hepatic stellate cells (HSCs) were activated and secreted excessive amounts of extracellular matrix (ECM) proteins during pathogenetic progress of liver fibrosis. Germacrone (GMO) and miR-29b can play an important role in inhibiting growth of HSCs and production of type I collagen. GMO and miR-29b were co-encapsulated into nanoparticles (NPs) based on poly(ethylene glycol)-block-poly(lactide-co-glycolide) (PEG-PLGA). Then, NPs were modified with cyclic RGD peptides (cRGDfK). cRGDfK is an effective ligand to bind integrin αvβ3 and increase the targeting ability for fibrotic liver. GMO- and miR-29b-loaded NPs exhibited great cytotoxicity to activated HSCs and significantly inhibited production of type I collagen. Liver fibrosis model of mice was induced by administration of carbon tetrachloride. Great targeting ability was achieved in liver fibrotic mice treated with cRGD-modified NPs. Significant ant-fibrotic effects have been presented based on hematoxylin and eosin (H&E), Masson and Sirius Red staining results of liver tissues collected from mice treated with drug-loaded NPs. All these results indicate GMO- and miR-29b-loaded cRGD-modified NPs have the potential for clinical use to treat liver fibrosis. [ABSTRACT FROM AUTHOR]

There are around 140 species in the genus Callicarpa, with 23 species occurring in Vietnam. The Vietnamese Callicarpa species have been poorly studied. In this work, the leaf essential oils of C. bodinieri, C. candicans, C. formosana, C. longifolia, C. nudiflora, C. petelotii, C. rubella, and C. sinuata, have been obtained from plants growing in central Vietnam. The chemical compositions of the essential oils were determined using gas chromatography – mass spectrometry. Mosquito larvicidal activities of the essential oils were carried out against Aedes aegypti. All of the Callicarpa leaf essential oils showed larvicidal activity, but two samples of C. candicans were particularly active with 48-h LC50 values of 2.1 and 3.8 μg/mL. Callicarpa candicans essential oil should be considered as a potential alternative mosquito control agent. [ABSTRACT FROM AUTHOR]

The aim of the present study was to investigate the effects of germacrone (GM) and dexmedetomidine (DEX) in treating type 2 diabetes mellitus (T2DM). A high-fat diet (HFD)-induced T2DM rat model was established. The experimental rats were divided into the control group, HFD group, GM treatment group, DEX treatment group and GM + DEX treatment group. In addition, adenosine monophosphate-activated protein kinase (AMPK) inhibitor compound C (CC) was used to inhibit AMPKα1 expression. All rats received their respective treatment daily for 21 days. Blood glucose and lipid levels, apoptosis of hepatic cells, and levels of inflammatory factors and oxidative stress indicators in serum samples were evaluated. Protein expression of AMPKα1 and its downstream targets were also investigated. Results demonstrated that blood glucose concentration, blood lipid indicators (endothelin, total cholesterol, triglyceride and low density lipoprotein cholesterol), cell apoptosis in liver tissues, total oxidant status, malondialdehyde, interleukin (IL)-6, tumor necrosis factor-α (TNF-α) and IL-1β levels in serum were increased in the high-fat group compared to the control but decreased following GM and/or DEX treatment. By contrast, high-density lipoprotein cholesterol and antioxidative stress indicator superoxide dismutase (SOD) were decreased in the high-fat group but increased following GM and/or DEX treatment. Protein expression of AMPKα1 and the catabolic genes carnitine palmitoyltransferase-1, peroxisome proliferator-activated receptor-α and acyl coenzyme A were decreased whilst anabolic genes, including sterol regulatory element binding protein-1c, fatty acid synthase and diacylglycerol acyltransferase-2, were increased in the HFD group. These effects were attenuated by GM and/or DEX treatment. AMPKα1 inhibition resulted in decreased SOD and increased cell apoptosis in liver tissues as well as increased IL-6, TNF-α and IL-1β levels compared with the HFD group. However, these effects were abolished following treatment with CC, GM and DEX together. Taken together these results indicated that GM worked synergistically with DEX to attenuate symptoms of high-fat-induced T2DM, with the effect potentially involving an increase in AMPKα1 expression. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease. The imbalance of T helper type 1 (Th1) and Th2 immune responses contributes to the pathogenesis of this disease. Germacrone is a major bioactive component isolated from Rhizoma Curcuma with multiple bioactivities including anti-inflammation. However, the role and mechanism of germacrone in RA are still unknown. Collagen-induced arthritis (CIA) model was established in male DBA/1 J mice by two immunizations with chicken collagen II. Germacrone was orally administered once per day starting on the day of second immunization for 3 weeks. Arthritis scoring was evaluated every 3 days after second immunization. H&E staining was used for histopathological examination. Levels of tumor necrosis factor (TNF)-α, interferon (IFN)-γ and interleukin (IL)-4 in serum and synovial tissues of mice were detected by ELISA. Th1 and Th2 cell percentage in mouse spleens was analyzed by flow cytometry. IκB and phosphorylation of NF-κB p65 (p-p65) expression in mouse synovial tissues was assayed by Western blot. We found germacrone treatment significantly reduced arthritis score and inflammation in CIA mice. Levels of TNF-α and IFN-γ were elevated, and IL-4 reduced, in the serum and synovial tissues of CIA mice. Germacrone partially reversed levels of these cytokines. Moreover, germacrone decreased the ratio of Th1 to Th2 cells in mouse spleens. Additionally, germacrone remarkably enhanced IκB expression, but suppressed p-p65 level in CIA mice. Taken together, these results suggest that germacrone alleviated the progression of arthritis that might be related to the regulation of Th1/Th2 balance and inactivation of NF-κB pathway. • Germacrone alleviated the progression of arthritis. • Germacrone could reduce Th1 cytokines and increase Th2 cytokines. • Germacrone decreased Th1/Th2 ratio in CIA mice. • Germacrone suppressed the activation of NF-κB in synovial tissues. [ABSTRACT FROM AUTHOR]

The aim of this research was to isolate and indentify the terpenoid compound from Curcuma xanthorrhiza rhizomes and its antibacterial activity. Isolation was carried out by using vacuum liquid chromatography and centrifugal chromatography. The structure was determined by NMR spectroscopy (1H-NMR, 13C-NMR 1D and 2D), then compare with data from literatures. Antibacterial test was carried out by using microdillution methods and evaluated against eight bacteria. They are Bacillus subtilis, Staphylococcus aureus, Escherichia coli, Enterobacter aerogenes, Pseudomonas aeruginosa, Salmonella typhi, Shigella dysentriae and Vibrio cholerae. The result showed that the isolate was a white crystal which was indetified as germacron-type sesquiterpene. Germacron have highest activity againts P. aeruginosa, MIC 15.6 µg/mL and MBC 31.2 µg/mL.

Background: Germacrone, a naturally occurring active compound found in essential oils extracted from medicinal plants within the Zingiberaceae family, has garnered attention for its potential therapeutic applications. Extensive research has highlighted its multi-targeting capabilities, positioning it as a promising treatment for various chronic diseases, including cancer, cardiovascular conditions, and neurodegenerative disorders like Alzheimer's disease., Objective: This review aims to provide a comprehensive overview of germacrone as a scaffold for developing multi-targeting drugs with therapeutic potential against a range of chronic disorders. The study delves into the molecular mechanisms that underlie the therapeutic effects of germacrone and explores its potential targets, including NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction., Methods: A systematic review of literature databases was conducted to gather relevant studies on germacrone and its therapeutic applications. The molecular mechanisms and potential targets of germacrone were examined to elucidate its multi-targeting capabilities., Results: Germacrone exhibits significant potential in the management of chronic diseases, with demonstrated effects on various cellular pathways. The review highlights its impact on NF-κB, PI3K/AKT/mTOR, p53, JAK/STAT, caspase, apoptosis, and autophagy induction, showcasing its versatility in targeting multiple pathways associated with chronic conditions. Germacrone has emerged as a promising candidate for the treatment of diverse chronic diseases. The understanding of its multi-targeting capabilities, coupled with its natural origin, positions it as a valuable scaffold for developing therapeutics., Conclusion: The exploration of germacrone as a structural framework for multi-targeting drugs offers a potential avenue to enhance efficacy while minimizing potential side effects. Further research and clinical trials are warranted to validate the therapeutic potential of germacrone in diverse medical contexts., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

The insecticidal and acaricidal effects of the essential oils (EO) from two populations of Geranium macrorrhizum L (ornamental variety Bevan, VB and wild population from Hungary, GH) have been studied against several insect pests of economic importance in agriculture ( Spodoptera littoralis , Myzus persicae and Rhopalosiphum padi ), and the hard tick Hyalomma lusitanicum . The oil from the wild population (GH) was characterized by its content in β-elemenone (30.53%), thymol (18.52%) and germacrone (15.54%), while the oil from the commercial variety (VB) had linalool (26.45%) and linalyl acetate (25.11%) as major components. S.litoralis and R. padi were significantly affected by the wild population oil (GH-EO). The oil from the commercial variety VB was less effective against insects. The ixodicidal effects of these oils were strong, being the wild population (GH-EO) the most effective. To correlate the composition of these oils with their activity, the essential oil major components have been isolated (germacrone and β-elemenone) and tested (linalool, thymol, germacrone and β-elemenone). The insect antifeedant and ixodicidal effects of thymol and germacrone explained the bioactivity of the GH essential oil. Therefore, the wild variety of G. macrorrhizum has been selected for domestication given its potential as a source of bioactive extracts and metabolites. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) usually causes chemotherapy failure of chronic myelogenous leukemia (CML). Germacrone is a terpenoid compound and has been reported to reverse MDR in breast cancer cells. However, the effect of germacrone on MDR in CML cells was unknown. The aim of the present study was to evaluate the effect of germacrone on MDR in adriamycin resistance of CML cells. Treatment with a combination of germacrone and adriamycin synergistically inhibited the viability and increased LDH release in K562/ADM cells. Adriamycin induced the apoptosis and caspase-3 activity of K562/ADM cells, and the germacrone treatment significantly enhanced the induction. Adriamycin treatment inhibited the expression of Bcl-2 and induced the expression of Bax, and germacrone enhanced the effect of adriamycin. Germacrone decreased adriamycin-induced expression of MDR1 mRNA and P-gp protein. Overexpression of P-glycoprotein (P-gp) reversed the effect of germacrone on adriamycin resistance in K562/ADM cells. In conclusion, germacrone reversed adriamycin resistance in human chronic myelogenous leukemia K562/ADM cells by suppressing MDR1 gene/P-gp expression. The results indicated that germacrone might be a new MDR reversal agent for CML chemotherapy. [ABSTRACT FROM AUTHOR]

• Germacrone alleviates cardiac remodeling and heart failure. • Germacrone inhibits the oxiditative stress, inflammatory response, and apoptosis during cardiac remodeling. • The PI3K/AKT signaling pathway is crucial for the cardioprotective effect of germacrone. Cardiac remodeling is a common consequence of cardiovascular diseases and is closely associated with oxidative stress, inflammation, and apoptosis. Germacrone, a bioactive compound present in Rhizoma curcuma , has been shown to possess anti-oxidative, anti-inflammatory, and anti-apoptotic properties. The aim of this study was to investigate the protective effect of germacrone against cardiac remodeling. Here, C57BL/6 mice were subcutaneous injection with isoproterenol (ISO) once daily for two weeks and were concurrent intragastric injection of germacrone. In vitro, neonatal rat cardiomyocytes (NRCMs) were used to verify the protective effect of germacrone on ISO-induced cardiac injury. Our findings indicated that ISO induce oxidative stress, inflammation, and apoptosis in vivo and in vitro , while germacrone treatment significantly attenuates these effects, thereby attenuating myocardium remodeling and cardiac dysfunction. Mechanistically, germacrone reduced cardiac remodeling-induced activation of phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway, and the cardioprotective effects of germacrone were abrogated by a PI3K agonist. In conclusion, our results suggest that germacrone attenuates oxidative stress, inflammation, and apoptosis in cardiac remodeling by inhibiting the PI3K/AKT pathway, and may therefore represent a promising therapeutic approach for the treatment of cardiac remodeling. [ABSTRACT FROM AUTHOR]

Pseudorabies virus (PRV), a member of the Herpesviridae, is the causative agent of an acute infectious disease in a variety of animals. The emergence of a novel variant strain brought huge economic losses to the pig industry since classical vaccine strains were not completely effective against variant strains. Therefore, the development of new anti-pseudorabies virus drugs and vaccines is of great significance for the treatment and prevention of pseudorabies. In this study, we found that germacrone, one of the major components of the essential oils extracted from Rhizoma Curcuma, was able to effectively inhibit PRV replication in a dose-dependent manner in vitro. Germacrone showed antiviral activity against PRV in the early phase of the viral replication cycle. Moreover, we found that germacrone does not directly kill the virus, nor does it affect the expression of the PRV receptor protein nectin-1, nectin-2, and CD155. Our results suggest germacrone could be used as an efficient microbicide or immunomodulatory agent in the control of the emerging variant PRV.

Minoxidil is approved for topical treatment of androgenic alopecia but hampered by poor cutaneous absorption. Recently, the randomized control trial showed that hair loss treatment of minoxidil was improved by co-application of the anti-androgen, Curcuma aeruginosa Roxb. extract. Here, we aimed to show that the apparent synergism arises from improved cutaneous penetration of minoxidil by bioactive compound, germacrone or C. aeruginosa (as an n-hexane extract, or essential oil). The partition coefficient of germacrone was determined by HPLC. Skin penetration was measured ex vivo on Franz diffusion cells using full thickness human foreskin as membranes. The receiver solution was sampled hourly for 8 h after which the skin was removed, the stratum corneum separated, and minoxidil assayed in this and in the remaining viable skin layer by HPLC. Skin penetration of minoxidil with 0.2 and 2% extract was increased ~ 4-fold (accumulated amount in receiver + skin viable layer after 8 h). Furthermore, germacrone enhanced minoxidil flux by ~ 10-fold and C. aeruginosa essential oil by ~ 20-fold. This work suggests three clinical consequences: (i) minoxidil efficacy is promoted, (ii) lower doses of minoxidil suffice, and (iii) C. aeruginosa extract/essential oil or germacrone can supplement treatment outcomes by acting as anti-androgen, thereby introducing a more effective topical treatment strategy for androgenic alopecia. [ABSTRACT FROM AUTHOR]

The chemical composition of leaf essential oil ofVepris unifoliolatawas characterized by hydrocarbon monoterpenes, α-pinene (60.5%), myrcene (6.8%), limonene (5.1%), (E)-β-ocimene (4.9%) and β-phellandrene (4.7%). The chemical composition of bark essential oil ofV. unifoliolatawas original and characterized by a high content in heat-sensitive compounds isofuranodiene (43.9%) and germacrone (17.1%). These compounds bearing the(E,E)-1,5-cyclodecadiene structure were known to rearrange and degrade during the GC–FID and GC-MS. The true content of isofuranodiene/curzerene, germacrone/trans-β-elemenone, germacrene A/β-elemene and germacrene B/γ-elemene was evaluated by combination of13C-NMR data (intensities of signals of selected carbons) and GC–FID. Thus, a correct quantitative analysis of bark oil ofV. unifoliolatawas provided.ABSTRACT FROM PUBLISHERCopyright of Journal of Essential Oil Research is the property of Taylor & Francis Ltd and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. [ABSTRACT FROM AUTHOR]