Costunosides A-C: cytotoxic sesquiterpene lactones from the rhizomes of Aucklandia costus Falc.

Three new eudesmane type rare sesquiterpene lactone galactosides, costunosides A-C (1-3) were isolated from the rhizomes of Aucklandia costus along with ten known compounds (4-13). Costunosides A-C (1-3) are the first example of naturally eudesmane glycosides containing a ß-galactopyranoside moiety. The structure and relative configurations of these compounds were established by comprehensive analysis of MS and, in particular 1D/2D NMR spectroscopic data. The isolated compounds were tested against a panel of human cancer cell lines, where compounds 3, 6 and 7 have shown promising cytotoxic activity against PC-3, HCT-116 and A549 cell lines with IC50 values in the range of 3.4 µM to 9.3 µM, respectively. Costunosides A-C (1-3) were also screened for inhibition assay of acetyl-cholinesterase (AChE), and butyrylcholinesterase (BChE) and found inactive at a concentration of 10 µM.

HPLC-PDA Method for Quantification of Bioactive Compounds in Crude Extract and Fractions of Aucklandia costus Falc. and Cytotoxicity Studies against Cancer Cells.

Aucklandia costus Falc. (Synonym: Saussurea costus (Falc.) Lipsch.) is a perennial herb of the family Asteraceae. The dried rhizome is an essential herb in the traditional systems of medicine in India, China and Tibet. The important pharmacological activities reported for Aucklandia costus are anticancer, hepatoprotective, antiulcer, antimicrobial, antiparasitic, antioxidant, anti-inflammatory and anti-fatigue activities. The objective of this study was the isolation and quantification of four marker compounds in the crude extract and different fractions of A. costus and the evaluation of the anticancer activity of the crude extract and its different fractions. The four marker compounds isolated from A. costus include dehydrocostus lactone, costunolide, syringin and 5-hydroxymethyl-2-furaldehyde. These four compounds were used as standard compounds for quantification. The chromatographic data showed good resolution and excellent linearity (r2 ˃ 0.993). The validation parameters, such as inter- and intraday precision (RSD < 1.96%) and analyte recovery (97.52-110.20%; RSD < 2.00%),revealed the high sensitivity and reliability of the developed HPLC method. The compounds dehydrocostus lactone and costunolide were concentrated in the hexane fraction (222.08 and 65.07 µg/mg, respectively) and chloroform fraction (99.02 and 30.21 µg/mg, respectively), while the n-butanol fraction is a rich source of syringin (37.91 µg/mg) and 5-hydroxymethyl-2-furaldehyde (7.94 µg/mg). Further, the SRB assay was performed for the evaluation of anticancer activity using lung, colon, breast and prostate cancer cell lines. The hexane and chloroform fractions show excellent IC50 values of 3.37 ± 0.14 and 7.527 ± 0.18 µg/mL, respectively, against the prostate cancer cell line (PC-3).

Trilliumosides K and L, two novel steroidal saponins from rhizomes of Trillium govanianum, as potent anti-cancer agents targeting apoptosis in the A-549 cancer cell line.

Two novel steroidal saponins, trilliumosides K (1) and L (2), were isolated from the rhizomes of Trillium govanianum led by bioactivity-guided phytochemical investigation along with seven known compounds: govanoside D (3), protodioscin (4), borassoside E (5), 20-hydroxyecdysone (6), 5,20-hydroxyecdysone (7), govanic acid (8), and diosgenin (9). The structure of novel compounds 1-2 was established using analysis of spectroscopic data including 1D and 2D nuclear magnetic resonance (NMR) and high resolution mass spectrometry (HR-ESI-MS) data. All isolated compounds were evaluated for in vitro cytotoxic activity against a panel of human cancer cell lines. Compound 1 showed significant cytotoxic activity against the A-549 (Lung) and SW-620 (Colon) cancer cell lines with IC50 values of 1.83 and 1.85 µM, respectively whereas the IC50 value of Compound 2 against the A-549 cell line was found to be 1.79 µM. Among the previously known compounds 3, 5, and 9, the cytotoxic IC50 values were found to be in the range of 5-10 µM. Comprehensive anti-cancer investigation revealed that Compound 2 inhibited in vitro migration and colony-forming capability in the A-549 cell line. Additionally, the mechanistic analysis of Compound 2 on the A-549 cell line indicated distinctive alterations in nuclear morphology, increased reactive oxygen species (ROS) production, and decreased levels of mitochondrial membrane potential (MMP). By upregulating the pro-apoptotic protein BAX and downregulating the anti-apoptotic protein BCL-2, the aforementioned actions eventually cause apoptosis, a crucial hallmark in cancer research, which activates Caspase-3. To the best of our knowledge, this study reports the first mechanistic anti-cancer evaluation of the compounds isolated from the rhizomes of T. govanianum with remarkable cytotoxic activity in the desired micromolar range.