| Description: |
Hecogenin, a steroid saponin isolated from Agave sisalana, is a potent and highly selective inhibitor of UGT1A4 with an IC50 value of 1.5 μM. Hecogenin has anti-cancer, antiproliferative,antioxidant and anti-inflammatory effects, it
can protect gastro by K⁺(ATP) channels opening and the COX-2/PG pathway. Hecogenin has inhibition of human rheumatoid arthritis synovial cell survival, the effect is associated with increased apoptosis, p38 mitogen-activated protein kinase activity and upregulation of cyclooxygenase-2.
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| Targets: |
ERK | MMP(e.g.TIMP) | COX | ATPase | Potassium Channel | p38MAPK | NO | TRPV | TNF-α | PGE | IL Receptor | PPAR | NF-kB | JNK |
| In vitro: |
| Anticancer Agents Med Chem. 2014;14(8):1128-35. | | Hecogenin acetate inhibits reactive oxygen species production and induces cell cycle arrest and senescence in the A549 human lung cancer cell line.[Pubmed: 25115457] | Cellular and molecular mechanisms related to lung cancer have been extensively studied in recent years, but the availability of effective treatments is still scarce. Hecogenin acetate, a natural saponin presenting a wide spectrum of reported pharmacological activities, has been previously evaluated for its anticancer/antiproliferative activity in some in vivo and in vitro models.
METHODS AND RESULTS:
Here, we investigated the effects of hecogenin acetate in a human lung cancer cell line. A549 non-small lung cancer cells were exposed to different concentrations of hecogenin acetate and reactive species production, ERK1/2 activation, matrix metalloproteinase expression, cell cycle arrest and cell senescence parameters were evaluated. Hecogenin acetate significantly inhibited increase in intracellular reactive species production induced by H2O2. In addition, hecogenin acetate blocked ERK1/2 phosphorylation and inhibited the increase in MMP-2 caused by H2O2. Treatment with hecogenin acetate induced G0/G1-phase arrest at two concentrations (75 and 100 μM, 74% and 84.3% respectively), and increased the staining of senescence-associated β -galactosidase positive cells.
CONCLUSIONS:
These data indicate that hecogenin acetate is able to exert anti-cancer effects by modulating reactive species production, inducing cell cycle arrest and senescence and also modulating ERK1/2 phosphorylation and MMP-2 production. | | Int J Mol Med. 2007 Oct;20(4):451-60. | | Inhibition of human rheumatoid arthritis synovial cell survival by hecogenin and tigogenin is associated with increased apoptosis, p38 mitogen-activated protein kinase activity and upregulation of cyclooxygenase-2.[Pubmed: 17786275] | We conducted our study to assess the antiproliferative and proapoptotic potential of hecogenin and tigogenin, two saponins which are structurally similar to diosgenin. We particularly focused our attention on mitogen-activated protein kinase (MAPK) activation in relation to apoptosis but also with the COX-2 expression and activity. Rheumatoid arthritis (RA) synoviocytes were isolated from fresh synovial biopsies obtained from five RA patients undergoing hip arthroplasty.
METHODS AND RESULTS:
Measurement of cell proliferation was determined using the MTT assay. Apoptosis was evaluated by studying caspase-8, caspase-9 and caspase-3 activities but also by quantification of DNA fragmentation. Quantification of human phospho-MAPKs was realized by ELISA. COX-2 expression was demonstrated by Western blot analysis and COX-2 activity by assay of endogenous prostaglandin E2 (PGE2) production. Tigogenin was more effective than hecogenin in inducing apoptosis in human RA fibroblast-like synoviocytes (FLS) which was caspase dependent but poly(ADP-ribose) polymerase independent and characterized by DNA fragmentation. Our results demonstrated hecogenin- and tigogenin-induced apoptosis through activation of p38 without affecting the JNK and ERK pathways. Indeed, pretreatment with a p38 inhibitor decreased saponin-induced apoptosis with a significant decrease in DNA fragmentation. Furthermore, the rate of apoptosis induced by hecogenin or tigogenin was associated with overexpression of COX-2 correlated with overproduction of endogenous PGE2.
CONCLUSIONS:
These new results provide strong evidence that a family of structurally similar plant steroids is capable of inducing apoptosis in human RA FLS with different rates and different signalling pathways.
This study also confirms the discussed appearance of the downregulation or upregulation of COX-2 in cell apoptosis as a function of cell type. |
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| In vivo: |
| Molecules. 2014 Jun 19;19(6):8303-16. | | Evidence for the involvement of spinal cord-inhibitory and cytokines-modulatory mechanisms in the anti-hyperalgesic effect of hecogenin acetate, a steroidal sapogenin-acetylated, in mice.[Pubmed: 24950436] | Hecogenin is a steroidal sapogenin largely drawn from the plants of the genus Agave, commonly known as 'sisal', and is one of the important precursors used by the pharmaceutical industry for the synthesis of steroid hormones. Hecogenin acetate (HA) is a steroidal sapogenin-acetylated that produces antinociceptive activity.
Thus, we evaluate the antihyperalgesic profile of HA in mice in inflammatory models, as well as its possible involvement with c-fos expression on spinal cord area and cytokines to produces analgesic profile.
METHODS AND RESULTS:
Acute pretreatment with HA (5, 10, or 20 mg/kg; i.p.) inhibited the development of mechanical hyperalgesia induced by carrageenan, TNF-α, dopamine and PGE2. Additionally, the immunofluorescence data demonstrated that acute pretreatment with HA, at all doses tested, significantly inhibited Fos-like expression in the spinal cord dorsal horn normally observed after carrageenan-inflammation. Moreover, HA did not affect the motor performance of the mice as tested in the Rota rod test. This antinociceptive profile seems to be related, at least in part, to a reduction of pro-inflammatory cytokines, as IL-1β.
CONCLUSIONS:
The present results suggest that HA attenuates mechanical hyperalgesia by blocking the neural transmission of pain at the spinal cord levels and by cytokines-inhibitory mechanisms. |
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