(R)-(-)-Xanthorrhizol Inhibits the Migration and Invasion of Triple-Negative Breast Cancer Cells by Suppressing Matrix Metalloproteinases via the NF-κB Signaling Pathway.

(R)-(-)-xanthorrhizol is a bioactive sesquiterpenoid and major chemical constituent of Curcuma zanthorrhiza rhizomes. It was reported to have many pharmacological activities including nephroprotective, hepatoprotective, antimicrobial, anti-inflammatory, antioxidant, antihypertensive, antihyperglycemic, antiplatelet, estrogenic, and antiestrogenic properties. (R)-(-)-xanthorrhizol was also investigated for antiproliferative activity against many cancer cells including breast, lung, liver, ovarian, and colon cancer. It was also revealed to have a potential effect on TNBC cells MDA-MB-231. Considering the previous studies, this study has aimed to investigate the antimigratory and anti-invasive properties, as well as the possible molecular mechanisms, behind these properties. The findings of (R)-(-)-xanthorrhizol on MDA-MB-231 cell migration and invasion demonstrated significant inhibition at three different concentrations in a concentration-dependent manner, which was observed in the scratch, transwell migration, and invasion assays. Further investigation of the molecular mechanism using gelatin zymography revealed that (R)-(-)-xanthorrhizol prevented cell migration and invasion of breast cancer cells through the inhibition of matrix metalloproteinase-2 and matrix metalloproteinase-9 expression. Western blot analysis indicated that the inhibition of matrix metalloproteinases is possibly the result of the inhibition of phosphorylation in the NF-κB signaling pathway. These findings corroborate (R)-(-)-xanthorrhizol to proceed for the further studies as a possible future drug candidate for cancer patients.

Antidepressant evaluation of Andrographis paniculata Nees extract and andrographolide in chronic unpredictable stress zebrafish model.

Andrographis paniculata (A. paniculata) showed an anti-depressive effect in rodent models. Zebrafish has recently emerged as a worthy complementary translational model for antidepressant drug discovery study. This study investigates the anti-depressive effect of A. paniculata extract and andrographolide in the chronic unpredictable stress (CUS)- zebrafish model. Four groups of zebrafish (n = 10/group), i.e. control, CUS (stressed, untreated), CUS + A. paniculata (100 mg/L) and CUS + fluoxetine (0.01 mg/L) were assessed in open-field and social interaction tests, 24 h after treatment. After extract screening, behavioural and cortisol analysis of andrographolide (5, 25 and 50 mg/kg, i.p.) and fluoxetine (10 mg/kg, i.p.) were evaluated. Before the behavioural study, acute toxicity and characterization of A. paniculata extract using UHPLC-ESI-MS/MS were performed. A significant reduction in freezing duration was found in A. paniculata- (t-test, p = 0.0234) and fluoxetine-treated groups (t-test, p < 0.0001) compared to the CUS group. A significant increase in total distance travelled, and contact duration was observed only in the fluoxetine-treated group (t-test, p = 0.0007) and (t-test, p = 0.0207), respectively. A significant increase in highly mobile duration was observed in both treatment groups. Andrographolide (50 mg/kg, i.p.) acute treatment showed a significant reduction in freezing duration (p = 0.0042), duration in a dark area (p = 0.0338) and cortisol level (p = 0.0156) and increased total distance travelled (p = 0.0144). Twenty-six compounds were tentatively characterized by LC-MS/MS method, and andrographolide content is 0.042 µg/g. According to cortisol analysis, A. paniculata's LC50 is 627.99 mg/L, while andrographolide's EC50 was determined as 26.915 mg/kg. Further assessment of the cellular and molecular underpinnings of the anti-depressive effect of andrographolide is strongly recommended to evaluate the potential as an antidepressant.

Bioactive compounds from Curcuma aeruginosa and the effect of comosone II on the migration and invasion of breast cancer cells.

Bioassay-guided separation afforded furanodienone 1,10-epoxide (9) as the new compound, curcolone (10) as partially described compound and ten known compounds; germacrone (1), furanodienone (2), curzerenone (3), curcumenol (4), zederone (5), comosone II (6), (1E,4E,8R)-8-hydroxygermacra-1(10),4,7(11)-trieno-12,8-lactone (7), 13-hydroxygermacrone (8), curcuzederone (11) and demethoxycurcumin (12). The study showed that germacrone, furanodienone, curzerenone, comosone II, 13-hydroxygermacrone, curcuzederone and demethoxycurcumin are the bioactive compounds of C. aeruginosa rhizomes. Comosone II significantly inhibited MDA-MB-231 cell migration and invasion through the inhibition of MMP-9 enzyme. The present study may lead to further anticancer studies of comosone II and supports the traditional uses of C. aeruginosa rhizomes.

Dimethyl-ammonium 5,5-dimethyl-3-oxo-2-(3,3,6,6-tetra-methyl-1,8-dioxo-2,3,4,5,6,7,8,9-octa-hydro-1H-xanthen-9-yl)cyclo-hex-1-enolate 9-(2-hydr-oxy-4,4-dimethyl-6-oxocyclo-hex-1-en-yl)-3,3,6,6-tetra-methyl-3,4,5,6,7,9-hexa-hydro-1H-xanthene-1,8(2H)-dione n-hexane hemisolvate monohydrate.

The main mol-ecule of the title compound, C(2)H(8)N(+)·C(25)H(31)O(5) (-)·C(25)H(32)O(5)·0.5C(6)H(14)·H(2)O, exists as two crystallographically independent mol-ecules, the hydr-oxy group of one being deprotonated. The pyran rings of both independent units adopt boat conformations. One of the two cyclo-hexene rings of the xanthene unit adopts an envelope conformation whereas the other is in a half-chair conformation. The cyclo-hexene ring attached to the xanthene unit adopts an envelope conformation. The n-hexane solvent mol-ecule is disordered about a crystallographic glide plane and the symmetry-independent components are again disordered over two positions, each with an occupancy of 0.25. In the crystal structure, the xanthene derivatives are linked by O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds, forming a three-dimensional network with channels along the a axis. The dimethyl-ammonium cations and water mol-ecules lie in small channels and are linked to the framework via O-H.·O and N-H⋯O hydrogen bonds. The n-hexane solvent mol-ecules occupy large channels.