Pristimerin CAS NO.1258-84-0

Pristimerin, a natural anti-tumor triterpenoid, inhibits LPS-induced TNF-α and IL-8 production through down-regulation of ROS-related classical NF-κB pathway in THP-1 cells.[Pubmed: 24957686]

Int Immunopharmacol. 2014 Aug;21(2):501-8.

Pristimerin, a naturally occurring quinonemethide triterpenoid compound, is known to exert a variety of pharmacological activities.
METHODS AND RESULTS:
In the present study, we investigated the molecular actions of Pristimerin against LPS-induced inflammatory responses in human monocytic THP-1 cells. The results showed that Pristimerin inhibited the production of TNF-α and IL-8 in a dose-dependent manner. To explore the possible mechanisms underlying these inhibitions by Pristimerin, we examined the intracellular ROS level and the NF-κB protein signaling pathway. Pristimerin clearly scavenged LPS-induced intracellular ROS production. In addition, Pristimerin prevented LPS-induced NF-κB activation through the inhibition of phosphorylation of IKKα/β, phosphorylation and degradation of IκBα, as well as phosphorylation and nuclear translocation of NF-κB p65.
CONCLUSIONS:
These findings suggest that Pristimerin down-regulates the expression of pro-inflammatory mediators through blocking of NF-κB activation by inhibiting interconnected ROS/IKK/NF-κB signaling pathways.

Antifungal properties of pristimerin and celastrol isolated from Celastrus hypoleucus.[Pubmed: 15593077 ]

Pest Manag Sci. 2005 Jan;61(1):85-90.

Pristimerin and celastrol isolated from the roots of Celastrus hypoleucus (Oliv) Warb f argutior Loes exhibited inhibitory effects against diverse phytopathogenic fungi.
METHODS AND RESULTS:
Pristimerin and celastrol were found to inhibit the mycelial growth of Rhizoctonia solani Kuhn and Glomerella cingulata (Stonem) Spauld & Schrenk in vitro by 83.6 and 62.6%, respectively, at 10 microg ml(-1). Pristimerin showed good preventive effect (96.7% at 100 microg ml(-1)) and curative effect (66.5% at 100 microg ml(-1)) against wheat powdery mildew in vivo. For celastrol, the preventive and curative effects against wheat powdery mildew were 80.5 and 45.4%, respectively, at 100 microg ml(-1).

Pristimerin, a naturally occurring triterpenoid, protects against autoimmune arthritis by modulating the cellular and soluble immune mediators of inflammation and tissue damage.[Pubmed: 25308129]

Clin Immunol. 2014 Dec;155(2):220-30.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder affecting the synovial joints. The currently available drugs for RA are effective only in a proportion of patients and their prolonged use is associated with severe adverse effects. Thus, new anti-arthritic agents are being sought.
METHODS AND RESULTS:
We tested Pristimerin, a naturally occurring triterpenoid, for its therapeutic activity against rat adjuvant arthritis. Pristimerin effectively inhibited both arthritic inflammation and cartilage and bone damage in the joints. Pristimerin-treated rats exhibited a reduction in the pro-inflammatory cytokines (IL-6, IL-17, IL-18, and IL-23) and the IL-6/IL-17-associated transcription factors (pSTAT3 and ROR-γt), coupled with an increase in the immunomodulatory cytokine IL-10. Also increased was IFN-γ, which can inhibit IL-17 response. In addition, the Th17/Treg ratio was altered in favor of immune suppression and the RANKL/OPG ratio was skewed towards anti-osteoclastogenesis.
CONCLUSIONS:
This is the first report on testing Pristimerin in arthritis. We suggest further evaluation of Pristimerin in RA patients.

Pristimerin, a quinonemethide triterpenoid, induces apoptosis in pancreatic cancer cells through the inhibition of pro-survival Akt/NF-κB/mTOR signaling proteins and anti-apoptotic Bcl-2.[Pubmed: 24603988]

Pristimerin enhances recombinant adeno-associated virus vector-mediated transgene expression in human cell lines in vitro and murine hepatocytes in vivo.[Pubmed: 24461592]

Inhibitory action of pristimerin on hypoxia?mediated metastasis involves stem cell characteristics and EMT in PC-3 prostate cancer cells.[Pubmed: 25571882]

Oncol Rep. 2015 Mar;33(3):1388-94.

The aim of the present study was to investigate whether Pristimerin affects the bone metastasis, stem cell characteristics and epithelial-mesenchymal transition (EMT) of prostate cancer (PCa) PC-3 cells subjected to hypoxia.
METHODS AND RESULTS:
The PC-3 cells were cultured under hypoxia or normoxia for 48 h and were then treated with increasing concentrations of Pristimerin from 0 to 0.8 μmol/l, under normoxia. Hypoxia?inducible factor-1α (HIF-1α) was detected by western blotting. Proliferation was assessed with the CCK-8 assay. Transwell invasion assay was used to analyze the potency of invasion. Stem cell characteristics were detected by sphere formation, colony formation assay and western blotting, including CD44, KLF4, OCT4 and AGO2, which are stem cell characteristic-related markers. EMT was confirmed by the expression changes of EMT-related markers, including N-cadherin, fibronectin, vimentin and ZEB1, which were evaluated by western blotting. The addition of Pristimerin to the medium reduced the hypoxia-induced PC-3 cell proliferation in a dose-dependent manner. Pristimerin effectively inhibited hypoxia?induced invasion of the PCa cells in vitro. Moreover, the treatment of cells with Pristimerin induced the reversal of hypoxia-induced stem cell characteristics and EMT, which was confirmed by sphere formation, colony formation assay and the expression changes of CSC- and EMT-related markers. The reversal of hypoxia?induced stem cell characteristics and EMT in the PCa cells by low-dose Pristimerin was dose?dependent.
CONCLUSIONS:
These results showed that treatment with Pristimerin may be a potential strategy for the suppression of hypoxia-induced metastasis through the reversal of hypoxia-induced stem cell characteristics and EMT in cancer cells, which justifies the potential use of Pristimerin as a practical chemopreventive approach for patients with PCa.

J Integr Med. 2014 Jan;12(1):20-34.

In the present study, we systemically evaluated the ability of two bioactive compounds from traditional Chinese medicine, celastrol and Pristimerin, to enhance recombinant adeno-associated virus (rAAV) serotype vector-mediated transgene expression both in human cell lines in vitro, and in murine hepatocytes in vivo.
METHODS AND RESULTS:
Human cell lines were infected with rAAV vectors with either mock treatment or treatment with celastrol or Pristimerin. The transgene expression, percentage of nuclear translocated viral genomes and the ubiquitination of intracellular proteins were investigated post-treatment. In addition, nonobese diabetic/severe combined immunodeficient gamma (NSG) mice were tail vain-injected with rAAV vectors and co-administered with either dimethyl sulfoxide, celastrol, Pristimerin or a positive control, bortezomib. The transgene expression in liver was detected and compared over time. We observed that treatment with Pristimerin, at as low as 1 μmol/L concentration, significantly enhanced rAAV2 vector-mediated transgene expression in vitro, and intraperitoneal co-administration with Pristimerin at 4 mg/(kg·d) for 3 d dramatically facilitated viral transduction in murine hepatocytes in vivo. The transduction efficiency of the tyrosine-mutant rAAV2 vectors as well as that of rAAV8 vectors carrying oversized transgene cassette was also augmented significantly by Pristimerin. The underlying molecular mechanisms by which Pristimerin mediated the observed increase in the transduction efficiency of rAAV vectors include both inhibition of proteasomal degradation of the intracellular proteins and enhanced nuclear translocation of the vector genomes.
CONCLUSIONS:
These studies suggest the potential beneficial use of Pristimerin and Pristimerin-containing herb extract in future liver-targeted gene therapy with rAAV vectors.

Int J Oncol. 2014 May;44(5):1707-15.

Lack of effective therapeutics for pancreatic cancer at the present time underscores the dire need for safe and effective agents for the treatment of this malignancy. In the present study, we have evaluated the anticancer activity and the mechanism of action of Pristimerin (PM), a quinonemethide triterpenoid, against MiaPaCa-2 and Panc-1 pancreatic ductal adenocarcinoma (PDA) cell lines.
METHODS AND RESULTS:
Treatment with Pristimerin inhibited the proliferation and induced apoptosis in both cell lines as characterized by the increased Annexin V-binding and cleavage of PARP-1 and procaspases -3, -8 and -9. Pristimerin also induced mitochondrial depolarization and the release of cytochrome c from the mitochondria. The induction of apoptosis by Pristimerin was associated with the inhibition of the pro-survival Akt, NF-κB and mTOR signaling proteins and their downstream intermediaries such as Foxo-3α and cyclin D1 (Akt); Cox-2 and VEGF (NF-κB); p-S6K1 and p-4E-BP1 (mTOR) as well as PKCε. Treatment with Pristimerin also inhibited the expression of anti-apoptotic Bcl-2 and survivin but not Bcl-xL. The downregulation of Bcl-2 by Pristimerin was not due to proteasomal or lysosomal proteolytic degradation of Bcl-2, since treatment with Pristimerin in the presence of proteasomal inhibitors MG132 or lactacystin (LAC) or calpain inhibitor MG101 failed to block the downregulation of Bcl-2 by Pristimerin. On the other hand, RT-PCR analysis showed the inhibition of Bcl-2 mRNA by Pristimerin in a dose-related manner, indicating that inhibition of Bcl-2 by Pristimerin is mediated through the suppression of Bcl-2 gene expression.
CONCLUSIONS:
Thus, the mechanistic understanding of the antitumor activity of Pristimerin could facilitate in vivo efficacy studies of Pristimerin for pancreatic cancer.