Triptolide is a diterpenoid triepoxide extracted from the root of Tripterygium wilfordii with immunosuppressive, anti-inflammatory and antiproliferative effects. Triptolide is a NF-κB activation inhibitor.
Isoalantolactone is an apoptosis inducer, which also acts as an alkylating agent.
Mogrol is a biometabolite of mogrosides, and acts via inhibition of the ERK1/2 and STAT3 pathways, or reducing CREB activation and activating AMPK signaling.
Genipin 1-β-D-gentiobioside (Genipin 1-gentiobioside) is one of the most abundant and bioactive iridoid glycosides in Gardenia jasminoides Ellis, which possesses hepatoprotective, anti-inflammatory, antioxidant, and antithrombotic activities.
Ginsenoside C-K, a bacterial metabolite of G-Rb1, exhibits anti-inflammatory effects by reducing iNOS and COX-2. Ginsenoside C-K exhibits an inhibition against the activity of CYP2C9 and CYP2A6 in human liver microsomes with IC50s of 32.0±3.6 μM and 63.6±4.2 μM, respectively.
Ajugol is an iridiod glucoside.
Glycyrrhizic acid is a triterpenoid saponinl, acting as a direct HMGB1 antagonist, with anti-tumor, anti-diabetic activities.
Atractylenolide III is a major component of Atractylodes rhizome can induce apoptosis of the lung carcinoma cells.IC50 value:Target: Anticancer natural compoundin vitro: ATL-III inhibited cell growth, increased lactate dehydrogenase release and modulated cell cycle on human lung carcinoma A549 cells. ALT-III induced the activation of caspase-3 and caspase-9 and cleavage of poly-(ADP)-ribose polymerase. ATL-III induced the release of cytochrome c, upregulation of bax expression, and translocation of apoptosis-inducing factor [1]. Atractylenolide II did not show cytoprotective effects, but oral administration of atractylenolide III dose-dependently prevented ethanol-induced PRGM cell death and cell membrane damage. The EC50 values were 0.27 and 0.34 mm, respectively [2]. Against adult D. pteronyssinus, atractylenolide III (LD50, 73.8 mg/m2) and atractylon (72.1 mg/m2) were eight times more active than Deet and 2.5-fold more toxic than dibutyl phthalate [3].in vivo: In the in-vivo assay, atractylenolide III 10 mg/kg significantly reduced 70% ethanol-induced Wistar rat gastric ulcer. Atractylenolide III could inhibit matrix metalloproteinase (MMP)-2 and MMP-9 expression through upregulation of tissue inhibitors of metalloproteinase from the gastric ulcerated tissues [2].
18β-Glycyrrhetinic acid is the major bioactive component of Glycyrrhizae Radix and possesses anti-ulcerative, anti-inflammatory and antiproliferative properties.
Ursolic acid(Bungeolic acid) is a natural pentacyclic triterpenoid carboxylic acid, exerts anti-tumor effects and is an effective compound for cancer prevention and therapy. IC50 value:Target:in vitro: UA induced phosphorylation of AMP-activated protein kinase alpha (AMPKα) and suppressed the protein expression of DNA methyltransferase 1 (DNMT1) in the dose-dependent manner [1]. The combination of ursolic acid (0.5 μM) and leucine (10 μM) proved to be the most effective in promoting myogenic differentiation. The combination of ursolic acid and leucine significantly increased CK activity than treatment with either agent alone. The level of myosin heavy chain, a myogenic differentiation marker protein, was also enhanced by the combination of ursolic acid and leucine [2]. Ursolic acid efficiently induced apoptosis, possibly via the downregulation of B-cell lymphoma 2 (Bcl-2), the upregulation of Bcl-2-associated X protein and the proteolytic activation of caspase-3. Furthermore, the activation of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase was increased by the administration of ursolic acid. In addition, ursolic acid significantly suppressed the invasive phenotype of the SNU-484 cells and significantly decreased the expression of matrix metalloproteinase (MMP)-2 [3]. ursolic acid (UA) potently induces the apoptosis of gastric cancer SGC-7901 cells. Further mechanistic studies revealed that the ROCK1/PTEN signaling pathway plays a critical role in UA-mediated mitochondrial translocation of cofilin-1 and apoptosis [4].in vivo: UA treatment markedly improved the survival of septic rats, and attenuated CLP-induced lung injury, including reduction of lung wet/dry weight ratio, infiltration of leukocytes and proteins, myeloperoxidase activity, and malondialdehyde content. In addition, UA significantly decreased the serum levels of tumor necrosis factor-α, interleukin-6, and interleukin-1β, inhibited the expression of inducible nitric oxide synthase and cyclooxygenase-2 in the lung, which are involved in the productions of nitric oxide and prostaglandin E2 [5].
Parthenolide is an NF-κB inhibitor, reduces histone deacetylase 1 (HDAC-1) and DNA methyltransferase 1 independent of NF-κB inhibition.
Farnesol is a sesquiterpene alcohol that modulates cell-to-cell communication in Candida albicans, and has the activity in inhibiting bacteria.
Ingenol is a PKC activator, with a Ki of 30 μM, with antitumor activity.
Alismoxide is a natural product.
Dipsacoside B is a major bioactive saponin, which can be used as a marker.
Astragaloside II is a natural isolated from Astragalus.IC50 value:Target:In vitro:In vivo: The developed and validated method has been successfully applied to the quantification and pharmacokinetic study of AST II in rats after intravenous and oral administration of AST II. The oral absolute bioavailability (F) of AST II was calculated to be 0.79 ± 0.16% with an elimination half-life (t1/2) value of 1.92 ± 0.30 h, suggesting its poor absorption and/or strong metabolism in vivo [1].
Betulinic acid is a natural pentacyclic triterpenoid, acts as a eukaryotic topoisomerase I inhibitor, with an IC50 of 5 μM, and possesses anti-HIV, anti-malarial, anti-inflammatory and anti-tumor properties.
Saikosaponin D is a triterpene saponin isolated from Bupleurum, with anti-inflammatory, anti-bacterial, anti-tumor, and anti-allergic activities; Saikosaponin D inhibits selectin, STAT3 and NF-kB and activates estrogen receptor-β.
Arglabin is a sesquiterpene gamma-lactone is isolated from Artemisia glabella; anticancer natural compound.IC50 value:Target: anticancerin vitro: Arglabin-stimulated macrophages displayed a strong cytotoxic activity and the lowest doses (1.25 micrograms/mL and 0.125 micrograms/mL) induced a significant stimulation of cell mitochondrial metabolism, which correlated with [3H]TdR uptake by J774.1 cells under the same experimental conditions. Arglabin triggered the production of the three cytokines from J774-1 cells. However, the pattern of cytokine secretion differed to some extent, according to the methodology used for cytokine measurement: either traditional bioassay or specific immunoassay (ELISA) [1]. Arglabin exhibits antiexudative and antiproliferative properties on the models of acute aseptic inflammation caused by formalin, carrageenan, and histamine, and on the model of proliferative inflammation accompanying cotton-pellet granuloma [2]. Arglabin is able to reduce the proportion of AML stem cells (CD34+CD38-) in primary AML cells [3].
Cephalomannine is a taxol derivative with antitumor, antiproliferative properties. IC50 value:Target: Cephalomannine is an active anti-cancer agent obtained from Taxus yunnanensis and has an antineoplastic effect on tumors found in mice. Cephalomannine is a chemotherapy drug that is given as a treatment for some types of cancer. Cephalomannine is most commonly used to treat non-small cell lung cancer.
Ginsenoside Rh4 is a rare saponin obtained from Panax notoginseng. Ginsenoside Rh4 activates Bax, caspase 3, caspase 8, and caspase 9. Ginsenoside Rh4 also induces autophagy.
Costunolide, a sesquiterpene lactone, exhibits anti-inflammatory and anti-oxidant properties and mediates apoptosis.IC50 Value: 6.2 - 9.8 ug/mL(sarcoma cells viability)[3]Target: Apoptosis inducerin vitro: Costunolide significantly inhibited RANKL-induced BMM differentiation into osteoclasts in a dose-dependent manner without affecting cytotoxicity. Costunolide did not regulate the early signaling pathways of RANKL, including the mitogen-activated protein kinase and NF-κB pathways. However, costunolide suppressed nuclear factor of activated T-cells, cytoplasmic 1 (NFATc1) expression via inhibition of c-Fos transcriptional activity without affecting RANKL-induced c-Fos expression. The inhibitory effects ofcostunolide were rescued by overexpression of constitutively active (CA)-NFATc1 [1]. Exposure of T24 cells to costunolide was also associated with increased expression of Bax, down-regulation of Bcl-2, survivin and significant activation of caspase-3, and its downstream target PARP [2]. Both costunolide and dehydrocostus lactone inhibited cell viability dose- and time-dependently. IC50 values ranged from 6.2 ug/mL to 9.8 ug/mL. Cells treated with costunolide showed no changes in cell cycle, little in caspase 3/7 activity, and low levels of cleaved caspase-3 after 24 and 48 h [3].in vivo: Neither costunolide nor alpha-MGBL affected the blood-ethanol elevation in pylorus-ligated rats or that induced by intraperitoneal and intraduodenal ethanol administration [4]. Costunolide and alpha-MGBL suppressed gastric emptying in rats given 20% ethanol and 1% sodium carboxymethyl cellulose.Clinical trial:
Ginsenoside Rd inhibits TNFα-induced NF-κB transcriptional activity with an IC50 of 12.05±0.82 μM in HepG2 cells. Ginsenoside Rd inhibits expression of COX-2 and iNOS mRNA. Ginsenoside Rd also inhibits Ca2+ influx. Ginsenoside Rd inhibits CYP2D6, CYP1A2, CYP3A4, and CYP2C9, with IC50s of 58.0±4.5 μM, 78.4±5.3 μM, 81.7±2.6 μM, and 85.1±9.1 μM, respectively.
Bevirimat(YK FH312; FH11327; MPC-4326) is an anti-HIV drug derived from a betulinic acid-like compound; is believed to inhibit HIV by a novel mechanism, so-called maturation inhibition.IC50 value:Target: Anti-HIVLike protease inhibitors, bevirimat and other maturation inhibitors interfere with protease processing of newly translated HIV polyprotein precursor, called gag. Bevirimat prevents this viral replication by specifically inhibiting cleavage of the capsid protein (CA) from the SP1 spacer protein.
Albiflorin is a major constituent contained in peony root; possesses therapeutic potential for neurodegenerative diseases.IC50 value:Target: in vitro: Albiflorin significantly ameliorated Glu-induced reduction of cell viability, nuclear and mitochondrial apoptotic alteration, reactive oxygen species accumulation, and B-cell lymphoma 2 (Bcl-2)/Bax ratio. Albiflorin also enhanced phosphorylation of AKT and its downstream element glycogen synthase kinase-3β, and this effect was abrogated by the AKT inhibitor LY294002 [1]. in vivo: Mice were exposed to X-ray radiation (400 Roentgen), and both mice and rabbits were intraperitoneally injected with cyclophosphamide (100.0 mg/kg) and cytarabine chloride (92.7 mg/kg), respectively, for 3 days to induce myelosuppression. Albiflorin was subsequently administrated intravenously at low (15.0 mg/kg for mice, 6.00 mg/kg for rabbits), intermediate (30.0 mg/kg for mice, 12.0 mg/kg for rabbits) and high (60.0 mg/kg for mice, 24.0 mg/kg for rabbits) doses, as well as orally (60.0 mg/kg for mice, 24.0 mg/kg for rabbits) for 7 days. Shenqi tablets were used as positive controls (oral administration of 936.0 mg/kg for mice, 336.0 mg/kg for rabbits). The administration of Albiflorin significantly ameliorated myelosuppression in all cases [2].
Astragaloside III is a natural product isolated from Astragalus.
Betulonic acid belongs to the pentacyclic triterpenic derivative class, has antitumor activities.In vitro: BEA-NP is found over three-times more permeable than that solubilized by DMSO in Caco-2 cell monocultures.[1]In vivo: The tumor growth in the S180 berry mice orally doses with BEA-NP at 75 mg/kg is inhibited by 50%. Rubusoside is effective in solubilizing BEA, maintaining its cytotoxicity, enhancing its permeability and reducing tumor growth when orally administered.[1] antitumor activities against MGC-803, PC3, Bcap-37, A375, and MCF-7 human cancer cell lines In vivo: The animals are treated with betulonic acid amide (50 mg/kg in Tween aqueous solution) and heptral (6 mg/kg) as hepatoprotective compounds. It is found that betulonic acid amide stimulats the regenerative response in hepatocytes under conditions of combined toxic exposure and promots recovery of their qualitative and quantitative characteristics. [2]
Quillaic acid(Quillaja sapogenin) is the major aglycone of the widely studied saponins of the Chilean indigenous tree Quillaja saponaria Mol; can elicit dose-dependent antinociceptive effects in two murine thermal models.
Astragaloside IV, an active component isolated from Astragalus membranaceus, suppresses the activation of ERK1/2 and JNK, and downregulates matrix metalloproteases (MMP)-2, (MMP)-9 in MDA-MB-231 breast cancer cells.
Pulchinenoside A is a natural triterpenoid saponin that enhances synaptic plasticity in the adult mouse hippocampus and facilitates spatial memory in adult mice.In vitro: Additions of pulsatilloside A and anemoside A3, at dosages ranging from 0.1, 1 and 10 μg/ml, protected PC12 cells from apoptosis. [1]In vivo:AA3 also acts as a non-competitive NMDA receptor (NMDAR) modulator with a neuroprotective capacity against ischemic brain injury and overexcitation in rats. [2] Anemoside A3 produces relaxation in rat renal arteries through multiple mechanisms. [3]