Artemether is an antimalarial for the treatment of resistant strains of falciparum malaria.Target: AntiparasiticArtemether is an antimalarial agent used to treat acute uncomplicated malaria. It is administered in combination with lumefantrine for improved efficacy. Artemether exhibits the highest activity against juvenile stages of the parasites, while adult worms are significantly less susceptible. There was no indication of neurotoxicity following repeated high doses of artemether given fortnightly for up to 5 months. Artemether-integrated with other control strategies-has considerable potential for reducing the current burden of schistosomiasis in different epidemiological settings [1]. There were remarkably inhibitory effects of artmeter on brain glioma growth and angiogenesis in SD rats and the mechanism that artemether inhibited brain glioma growth might be penetrating the blood-brain barrier and inhibiting angiogenesis [2].
Isosteviol is a derivative of stevioside, a constituent of Stevia rebaudiana, which is commonly used as a noncaloric sugar substitute in Japan and Brazil.Target:Isosteviol dose-dependently relaxed the vasopressin (10-8 M)-induced vasoconstriction in isolated aortic rings with or without endothelium. However, in the presence of potassium chloride (3×10-2 M), the vasodilator effect of isosteviol on arterial strips disappeared. Only the inhibitors specific for the ATP-sensitive potassium (KATP) channel or small conductance calcium-activated potassium (SKCa) channel inhibited the vasodilator effect of isosteviol in isolated aortic rings contracted with 10-8 M vasopressin [1]. The attenuation by isosteviol of the vasopressin- and phenylephrine-induced increase in [Ca (2+)]i was inhibited by glibenclamide, apamin and 4-aminopyridine but not by charybdotoxin. Furthermore, the inhibitory action of isosteviol on [Ca (2+)]i was blocked when A7r5 cells co-treated with glibenclamide and apamin in conjunction with 4-aminopyridine were present [2]. Isosteviol (1-100 micromol/l) inhibits angiotensin-II-induced DNA synthesis and endothelin-1 secretion. Measurements of 2'7'-dichlorofluorescin diacetate, a redox-sensitive fluorescent dye, showed an isosteviol-mediated inhibition of intracellular reactive oxygen species generated by the effects of angiotensin II [3].
Ginsenoside Rg2 is one of the major active components of ginseng. Ginsenoside Rg2 acts as a NF-κB inhibitor. Ginsenoside Rg2 also reduces Aβ1-42 accumulation.
Isoastragaloside I is a natural compound from the medicinal herb Radix Astragali; possesses the activity of elevating adiponectin production.IC50 value:Target:Astragaloside II and isoastragaloside I selectively increased adiponectin secretion in primary adipocytes without any obvious effects on a panel of other adipokines. Furthermore, an additive effect on induction of adiponectin production was observed between these two compounds and rosiglitazone, a thiazolidinedione class of insulin-sensitizing drugs. Chronic administration of astragaloside II and isoastragaloside I in both dietary and genetic obese mice significantly elevated serum levels of total adiponectin and selectively increased the composition of its high molecular weight oligomeric complex.
Corosolic acid isolated from the fruit of Cratoegus pinnatifida var. psilosa, was reported to have anticancer activity.IC50 value: 26.8 μg/ml in vitroTarget:In vitro: Corosolic acid displayed about the same potent cytotoxic activity as ursolic acid against several human cancer cell lines. In addition, the compound displayed antagonistic activity against the phorbol ester-induced morphological modification of K-562 leukemic cells, indicating the suppression of protein kinase C (PKC) activity by the cytotoxic compound. The compound showed PKC inhibition with dose-dependent pattern in an in vitro PKC assay [1]. MTT method was used to detect the influence of corosolic acid on A549 lung cancer cell growth in vitro under different concentrations. The value of IC50 was 26.8 μg/ml in vitro experiment. Corosolic acid of different doses had certain therapeutic effects on A549 solid tumor, the content of VEGF and CD34 proteins also had different degrees of influence [2]. Corosolic acid induced apoptosis in CT-26 cells, mediated by the activation of caspase-3. It inhibited the proliferation and tube formation of human umbilical vein endothelial cells and human dermal lymphatic microvascular endothelial cells, decreased the proliferation and migration of human umbilical vein endothelial cells stimulated by angiopoietin-1 [3]. In vivo: A mouse colon carcinoma CT-26 animal model was employed to determine the in vivo anti-angiogenic and anti-lymphangiogenic effects of corosolic acid.
Atractylenolide I is a sesquiterpene derived from the rhizome of Atractylodes macrocephala, possesses diverse bioactivities, such as neuroprotective, anti-allergic, anti-inflammatory and anticancer properties. Atractylenolide I reduces protein levels of phosphorylated JAK2 and STAT3 in A375 cells, and acts as a TLR4-antagonizing agent.
Oleanolic acid (Caryophyllin) is a natural compound from plants with anti-tumor activities.
Pachymic acid is a lanostrane-type triterpenoid from P. cocos. Pachymic acid inhibits Akt and ERK signaling pathways.
Cucurbitacin B belongs to a class of highly oxidized tetracyclic triterpenoids; could repress cancer cell progression.IC50 value:Target: anticancer natural compoundin vitro: Cucurbitacin-B inhibited growth and modulated expression of cell-cycle regulators in SHSY5Y cells. At the molecular level, we found that Cucurbitacin-B inhibited AKT signaling activation through up-regulation of PTEN [1]. CuB induced apoptosis of A549 cells in a -concentration-dependent manner, as determined by fluorescence microscopy, flow cytometry and transmission electron microscopy. CuB dose-dependently inhibited lung cancer cell proliferation, with cell cycle inhibition and cyclin B1 downregulation. Apoptosis induced by CuB was shown to be associated with cytochrome c release, B-cell lymphoma 2 downregulation and signal transducer and activator of transcription 3 pathway inhibition [2]. CuB inhibited ITGA6 and ITGB4 (integrin α6 and integrin β4), which are overexpressed in breast cancer. Furthermore, CuB also induced the expression of major ITGB1and ITGB3, which are known to cause integrin-mediated cell death [3]. Cuc B treatment caused DNA double-strand breaks (DSBs) without affecting the signal transducer and activator of transcription 3 (STAT3), the potential molecular target for Cuc B. Cuc B triggers ATM-activated Chk1-Cdc25C-Cdk1, which could be reversed by both ATM siRNA and Chk1 siRNA. Cuc B also triggers ATM-activated p53-14-3-3-σ pathways, which could be reversed by ATM siRNA [4].in vivo: Efficacy of CuB was tested in vivo using two different orthotopic models of breast cancer. MDA-MB-231 and 4T-1 cells were injected orthotopically in the mammary fat pad of female athymic nude mice or BALB/c mice respectively. Our results showed that CuB administration inhibited MDA-MB-231 orthotopic tumors by 55%, and 4T-1 tumors by 40%. The 4T-1 cells represent stage IV breast cancer and form very aggressive tumors [3].
Acetyl-11-Keto-β-Boswellic Acid (AKBA) is an active triterpenoid compound from the extract of Boswellia serrate; a novel Nrf2 activator.IC50 value:Target: Nrf2 activatorin vitro: AKBA significantly reduced infarct volumes and apoptotic cells, and also increased neurologic scores by elevating the Nrf2 and HO-1 expression in brain tissues in middle cerebral artery occlusion (MCAO) rats at 48 hours post reperfusion. In primary cultured neurons, AKBA increased the Nrf2 and HO-1 expression, which provided protection against OGD-induced oxidative insult. Additionally, AKBA treatment increased Nrf2 binding activity to antioxidant-response elements (ARE) [1]. AKBA significantly inhibited human colon adenocarcinoma growth, showing arrest of the cell cycle in G1-phase and induction of apoptosis[3]. AKBA triggered significant lipolysis in 3T3-L1 adipocytes as shown by reduced neutral lipids in cytosol and increased free fatty acids in culture medium. Increased lipolysis by AKBA was accompanied by up-regulation of lipolytic enzymes, adipocyte triglyceride lipase (ATGL) and hormone sensitive lipase (HSL), and a decreased expression of lipid droplet stability regulator perilipin. In addition, AKBA treatment reduced phenotypic markers of mature adipocyte aP2, adiponectin and glut-4 in mature adipocytes [5].in vivo: AKBA significantly prevented the formation of intestinal adenomatous polyps without toxicity to mice. AKBA's activity both in the prevention of small intestinal and colonic polyps was more potently than aspirin. Histopathologic examination revealed that AKBA's effect, that is the reduction of polyp size and degree of dysplasia, was more prominent in larger sized polyps, especially those originating in colon [2]. AKBA administration in mice effectively delayed the growth of HT-29 xenografts without signs of toxicity. The activity of AKBA was more potent than that of aspirin [3]. AKBA exhibited anti-cancer activity in vitro and in vivo. With oral application in mice, AKBA significantly inhibited SGC-7901 and MKN-45 xenografts without toxicity [4].
Phorbol is a highly toxic diterpene, whose esters have important biological properties.
Hederagenin is a triterpenoid saponin. It can inhibit LPS-stimulated expression of iNOS, COX-2, and NF-κBHederagenin can Exhibits multiple pharmacological activities in the treatment of hyperlipidemia, antilipid peroxidation, antiplatelet aggregation, liver protection, antidepression, anti-inflammation.[1]In vitro:1) Hederagenin can correct the imbalance of endothelial function by inhibiting the release of large amounts of iNOS and increasing eNOS contents and inhibits the IKKβ/NF-κB signaling pathway to reduce the release of IL-6, IFN-γ, TNF-α, and other inflammatory factors. [1]2) The EC50 of hederagenin is 39 ± 6 μM in A549 cancer cell line, but it's inactive for DLD-1 cells. [2]3) Hederagenin inhibited LPS-induced production of NO, PGE2and cytokines in cells.[3]4) Hederagenin had an anti-edema effect on the CA-induced mouse hind paw edema assay. [3]5) Hederagenin inhibited the CA-induced increase in skin thicknesses. [3]In vivo: The rats in the hederagenin group were administered hederagenin at 20 mg/kg/d via gavage.(More details please refer to the protocol below). In AS rat models induced by a high-lipid diet plus VD3, hederagenin can effectively reduce serum lipid, ALT, and AST levels, in addition to improving liver function, relieving high blood coagulation, and slowing blood flow and stasis by improving blood rheology. [1]
Beta Carotene is an organic compound and classified as a terpenoid. It is a precursor (inactive form) of vitamin A.Target: OthersBeta Carotene is a strongly colored red-orange pigment abundant in plants and fruits.β-Carotene is biosynthesized from geranylgeranyl pyrophosphate. It is a member of the carotenes, which are tetraterpenes, synthesized biochemically from eight isoprene units and thus having 40 carbons. Among this general class of carotenes, β-carotene is distinguished by having beta-rings at both ends of the molecule. Absorption of β-carotene is enhanced if eaten with fats, as carotenes are fat soluble [1, 2].
Atractylenolide II is a sesquiterpene compound isolated from the dried rhizome of Atractylodes macrocephala (Baizhu in Chinese); anti-proliferative activity.IC50 value: 82.3 μM(B16 melanoma cell, 48 h) [1]Target: anticancer natural compoundin vitro: AT-II treatment for 48 h dose-dependently inhibited cell proliferation with an IC(50) of 82.3 μM, and induced G1 phase cell cycle arrest. Moreover, treatment with 75 μM AT-II induced apoptosis. These observations were associated with the decrease of the expression of Cdk2, phosphorylated-Akt, phosphorylated-ERK and Bcl-2, the increase of the expression of phosphorylated-p38, phosphorylated-p53, p21, p27, and activation of caspases-8, -9 and -3. In addition, a chemical inhibitor of p53, PFTα, significantly decreased AT-II-mediated growth inhibition and apoptosis [1]. In B16 and A375 cells, AT-II (20, 40 μm) treatment for 48 h dose-dependently reduced protein expression levels of phospho-STAT3, phospho-Src, as well as STAT3-regulated Mcl-1 and Bcl-xL. Overexpression of a constitutively active variant of STAT3, STAT3C in A375 cells diminished the antiproliferative and apoptotic effects of AT-II [2].in vivo: Daily administration of AT-II (12.5, 25 mg/kg, i.g.) for 14 days significantly inhibited tumor growth in a B16 xenograft mouse model and inhibited the activation/phosphorylation of STAT3 and Src in the xenografts [2].
Ginsenoside Ro exhibits a Ca2+-antagonistic antiplatelet effect with an IC50 of 155 μM. Ginsenoside Ro reduces the production of TXA2 more than it reduces the activities of COX-1 and TXAS.
Notoginsenoside R1, the main bioactive component in panaxnotoginseng, is reported to have some neuronal protective, antihypertensive effects. IC50 value:Target:In vitro:In vivo: Notoginsenoside R1 significantly reduce blood pressure in spontaneously hypertensive rats and induce nitric oxide generation through increasing the phosphorylation of iNOS. Notoginsenoside R1 reduces the caudal blood pressure of spontaneously hypertensive rats through induction of iNOS regulated by long non-coding RNA AK094457 [1]. The mice with notoginsenoside R1 treatment showed significant amelioration in the cognitive function and increased choline acetyl transferase expression, as compared to the vehicle treated mice. Notoginsenoside R1 treatment inhibited Aβ accumulation and increased insulin degrading enzyme expression in both APP/PS1 mice and N2a-APP695sw cells [2]. In Notoginsenoside R1 treated rats, expression of TGF-β1and Smad3 at each time point was down-regulated, with statistical significance(P0.05) compared with that in the NDMA group [3].
Ginsenoside Rh1 is isolated from the root of Panax Ginseng. Ginsenoside Rh1 inhibits the expression of PPAR-γ, TNF-α, IL-6, and IL-1β.
Notoginsenoside R2 is a newly isolated notoginsenoside from Panax notoginseng, showed neuroprotective effects against 6-OHDA-induced oxidative stress and apoptosis.
Ginkgolide B, an important active terpenoid from Ginkgo biloba leaves, is reported to increase cell viability and decrease cell apoptosis.IC50 value:Target:In vitro: Ginkgolide B (0.2 or 0.4 μg/ml) was added to the culture medium in vitro led to increases in cell viability and decreases in the number of hippocampal cells undergoing AAPH-induced apoptosis [1]. Ginkgolide B caused a dose-related protection against dysrhythmias; the antiarrhythmic effect of ginkgolide B was comparable to that of diltiazem and superior to the activity of metoprolol. Ginkgolide B can presumably prevent the re-entry mechanism involved in the development of ischemia-induced rhythm disturbances [2].In vivo: Oral administration of ginkgolide B (2 mg/kg/day, p.o.) caused a significant increase in cell viability and a highly significant decrease in the numbers of both spontaneously occurring and AAPH-induced apoptoses.
Ginkgolide C is a flavone isolated from Ginkgo biloba leaves, possessing multiple biological functions, such as decreasing platelet aggregation and ameliorating Alzheimer disease.
Podocarpic acid is a natural product, which has the best all-round positive effect and acts as a novel TRPA1 activator.
Limonene is a monoterpene in citrus peel oil. A popular disinfectant and food preservative. Antimicrobial activities[1]. Anti-proliferative activities[2]. Antioxidant and anti-inflammatory effect[3].
Macranthoidin B is a major bioactive saponin in rat plasma after oral administration of extraction of saponins from Flos Lonicerae.
14-Deoxy-11,12-didehydroandrographolide is an analogue of Andrographolide that can be isolated from A. paniculata. 14-Deoxy-11,12-didehydroandrographolide inhibits NF-κB activation.
Ginsenoside Rb3 is extracted from steamed Panax notoginseng. Ginsenoside Rb3 exhibits inhibitory effect on TNFα-induced NF-κB transcriptional activity with an IC50 of 8.2 μM in 293T cell lines. Ginsenoside Rb3 also inhibits the induction of COX-2 and iNOS mRNA.
Curcumol is a sesquiterpene originally isolated from curcuma rhizomes; shows anticancer activities both in vitro and in vivo.IC50 value:Target: Anticancer natural compoundin vitro: Curcumol exhibited time- and concentration-dependent anti-proliferative effects in SPC-A-1 human lung adenocarcinoma cells with cell cycle arrest in the G0/G1 phase while apoptosis-induction was also confirmed with flow cytometry and morphological analyses [1]. Curcumol-induced growth inhibition correlated with apoptosis induction as evidenced by Annexin V staining, and cleavage of caspase-3 and poly (ADP-ribose) polymerase (PARP) in HSC-T6. Suppression of the NF-κB translocation via inhibition of IκB-α phosphorylation by the curcumol led to the inhibition of expression of NF-κB-regulated gene, e.g. Bcl-xL and Bcl-2, in a PI3K-dependent manner, which is upstream of NF-κB activation [2]. Curcumol exhibits an inhibitory effect on receptor activator of nuclear factor kappaB ligand (RANKL)-induced osteoclast differentiation with both bone marrow-derived macrophages and RAW264.7 cells in a dose-dependent manner [3].in vivo: Anti-neoplastic effects of curcumol were also confirmed in tumor bearing mice. Curcumol (60 mg/kg daily) significantly reduced tumor size without causing notable toxicity [1].
pleuromutilin inhibits bacterial protein synthesis by binding to the 50S ribosomal subunit of bacteria.
Acevaltrate, isolated from Valeriana glechomifolia, inhibits the Na+/K+-ATPase activity in the rat kidney and brain hemispheres with IC50s of 22.8±1.1 μM and 42.3±1.0 μM, respectively[1].
Cucurbitacin E is a natural compound which from the climbing stem of Cucumic melo L. Cucurbitacin E significantly suppresses the activity of the cyclin B1/CDC2 complex.
Gentiopicroside, a naturally occurring iridoid glycoside, inhibits P450 activity, with an IC50 and a Ki of 61 µM and 22.8 µM for CYP2A6; Gentiopicroside has antianti-inflammatoryand antioxidative effects.