U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

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Showing 11 - 20 of 25 results

Manumycin is a natural product isolated from Streptomyces parvulus. It has been reported to have anti-carcinogenic and anti-biotic properties. It acts as a potent and selective farnesyltransferase inhibitor. Manumycin inhibited PI3K-AKT activation and led to ROS accumulation and caspase-9 activation in the colorectal cancer cells. Manumycin induces apoptosis in malignant pleural mesothelioma through regulation of Sp1 and activation of the mitochondria-related apoptotic pathway. It is a potential to treat human oral squamous cell carcinoma via cell apoptosis through the downregulation of Sp1.
Diallyl disulfide (DADS) or allyl disulfide is the main organosulfur ingredient in garlic, with known antioxidant and anti-inflammatory activities. It has been shown to have multi-targeted antitumor activities in a variety of cancer cells Experiments in vitro have revealed, that diallyl disulfide inhibits the metastasis of type Ⅱ esophageal-gastric junction adenocarcinoma cells via NF-κB and PI3K/AKT signaling pathways. At the same time, was shown the drug suppresses cell stemness, proliferation, metastasis and glucose metabolism in breast cancer stem cells partly through the inhibition of CD44/PKM2/AMPK. Besides diallyl disulfide can be a promising agent for the treatment of emphysema, this was discovered in experiments on rats. And also drug shows protective effects against acetaminophen (AAP)-induced acute hepatotoxicity.
Dehydroabietic acid (DHA or DAA), a diterpene, is obtained from Commiphora oppbalsamum. DHA has potential as treatment for obesity and metabolic syndrome, obese diabetic KK-Ay mice treated with DHA showed decreased plasma glucose, insulin, and triglyceride levels. It has been reported that DHA inhibits the production of proinfammatory mediators such as TNF-α in macrophages and adipocytes and causes endothelium-dependent relaxation of pulmonary artery via PI3K/Akt-eNOS signaling pathway. Also was shown, that DHA could reverse several cell responses stimulated by TNF-α, including the activation of FOXO1 and the TGF-β1/Smad3 signaling pathway. Thus, DAA could be useful in improving the diabetic wound healing.
Ophiopogonin B is a glycosid (saponin) isolated from the butanol-soluble fraction of the fresh subterranean part of Ophiopogon japonicus, which is often used in Chinese traditional medicine to treat pulmonary disease and cancer. Ophiopogonin B was tested against non-small cell lung carcinoma, cervical cancer and gastric cancer cell lines, demonstrating inhibition of PI3K-Akt and mTOR-Akt signaling.
Alpha (α)-tomatine (simply tomatine) is the major saponin and occurs naturally in tomatoes, possesses a variety of biological properties including antioxidant, and anti-inflammatory. In additıon, tomatine is also known that it breaks down the cell membrane induces growth inhibition and apoptosis in different cancer cells: myeloid leukemia cells; prostate cancer cells; lung adenocarcinoma cells. However, the mechanisms of α-tomatine actions were not well understood. Nevertheless, was shown, that tomatine inhibited the NF-κB and phosphatidyl-inositol-3-kinase/Akt signaling pathways activation. However, the primary cellular target(s) for α-tomatine and its mechanisms for modulating apoptosis-associated pathways remain to be elucidated. The interaction of α-tomatine with cholesterol and the disruptive effect on the cell membrane may be one of the mechanisms by which α-tomatine induces apoptosis. The formation of complexes of α-tomatine and cholesterol may modulate the responsiveness of cell membrane receptors to growth stimuli and thus decrease the growth of cancer cells. Moreover, the anti-inflammatory mechanisms of α-tomatine, which may be a valuable therapeutic agent in the treatment of inflammation-related diseases was due to the ability of tomatine accelerated the phosphorylation of Akt in macrophages.
Nuciferine is an aporphine alkaloid extracted from lotus leaves, which is a raw material in Chinese medicinal herb for weight loss. Nuciferine was studied as an anti-tumor agent against human neuroblastoma and mouse colorectal cancer, through inhibiting the PI3K-AKT signaling pathways and IL-1 levels. In addition, was suggested, that nuciferine had atypical antipsychotic-like actions. Nuciferine was an antagonist at 5-HT2A, 5-HT2C, and 5-HT2B, an inverse agonist at 5-HT7, a partial agonist at D2, D5 and 5-HT6, an agonist at 5-HT1A and D4 receptors, and inhibited the dopamine transporter. In addition, was shown, that that nuciferine had a therapeutic effect on respiratory diseases associated with the aberrant contraction of airway smooth muscles and/or bronchospasm through the blockade of voltage-dependent L-type Ca2+ channels and/or nonselective cation channels.
Status:
Possibly Marketed Outside US

Class (Stereo):
CHEMICAL (ABSOLUTE)



Ruscogenin is a major steroid sapogenin found in the traditional Chinese medicinal herb Ophiopogon japonicus. It was first isolated from Ruscus aculeatus. Ruscogenin has multiple bioactivities and possesses a variety of pharmacological activities: anti-inflammatory properties, platelet aggregation inhibition, pulmonary hypertension lowering properties, acute lung injury alleviation and other effects. It was shown, that ruscogenin inhibited activation of neutrophil through cPLA2, PAK, Akt, MAPKs, cAMP, and PKA signaling pathways. In addition, Ruscogenin decreased expression of genes involved in hepatic lipogenesis through downregulation of NF-κB-mediated inflammatory responses. It was shown that ruscogenin significantly attenuate LPS-induced acute lung injury (ALI) via inhibiting expressions of TF and iNOS and NF-κB p65 activation, indicating it was a potential therapeutic agent for ALI or sepsis.
Status:
Possibly Marketed Outside US
Source:
Ginsamin Power by Biogrand Co., Ltd
Source URL:
First approved in 2010

Class (Stereo):
CHEMICAL (ACHIRAL)



Octacosanol, a low–molecular-weight primary aliphatic alcohol, is the main component of a natural product wax extracted from plants. Most studies have used a wheat-germ oil extract, or policosanol, a natural mixture of primary alcohols isolated from sugar cane wax, of which octacosanol is the main component (approximately 67% of policosanol is octacosanol). It has a number of indications for its use, many of which are currently being researched. Moreover, a small controlled study showed that some patients with mild Parkinsonism claimed of benefit from octacosanol. Although some research has been conducted using policosanol, little research is currently available that focuses on octacosanol alone. Studies have also found that octacosanol may inhibit the production of cholesterol. In the early 1990s, researchers at Dalmer Laboratories in La Habana Cuba isolated and produced the first policosanol (PC) supplement. The original PC supplement has been approved as a cholesterol-lowering drug in over 25 countries throughout the Caribbean and South America. Cuban studies claim that 1 to 20 mg/day of the original PC supplement are effective at producing significant reductions in total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C). These studies also show that PC supplements are potent antioxidants, promote proper arterial endothelial cell function, inhibit platelet aggregation and thrombosis, and serve as effective treatments for intermittent claudication. However, for the most part, those studies reporting therapeutic efficacy of PC were carried out by one research group situated in Cuba. Conversely, research groups outside of Cuba have failed to validate the cholesterol-lowering and antioxidant efficacy of PC. Cuban researchers, however, continue to claim that the efficacy is attributed to the unique purity and composition of the original PC preparation, a mixture not found in PC products used by external research groups. The absence of independent and external studies confirming the therapeutic benefits of PC in disease prevention and treatment raises questions regarding their true efficacy. Octacosanol also may prevent from atherosclerosis through activation of the PI3K/Akt and MAPK/Erk1/2 signaling pathways.
Oleanolic acid or oleanic acid is a naturally occurring pentacyclic triterpenoid. It is widely distributed in food and plants where it exists as a free acid or as an aglycone of triterpenoid saponins. Oleanolic acid protects the liver from acute chemically induced liver injury, fibrosis and cirrhosis caused by chronic liver diseases. Its possess cytotoxic activity against tumor cell lines
Status:
Possibly Marketed Outside US
Source:
NCT02200978: Phase 4 Interventional Completed Childhood Acute Promyelocytic Leukemia
(2011)
Source URL:

Class (Stereo):
CHEMICAL (ACHIRAL)



Tanshinone IIA is a derivative of phenanthrene-quinone isolated from Danshen, a widely used Chinese herbal medicine. It has antioxidant properties and cytotoxic activity against multiple human cancer cell lines, inducing apoptosis and differentiation of some human cancer cell lines. It was found, that tanshinone IIA might have potential anticancer activity on breast cancers through upregulation and downregulation of multiple genes involved in cell cycle regulation, cell proliferation, apoptosis, signal transduction, transcriptional regulation, angiogenesis, invasive potential and metastatic potential of cancer cells. ADPRTL1 might be the main target at which tanshinone IIA acted. Recently was discovered that tanshinone IIA exerts its cardio protective effects against H2O2-induced cell death by upregulating the expression of Bcl-2 via the activation of the PI3K/Akt signaling pathway, however, further studies are required in order to define and clarify the rationale for its clinical use.

Showing 11 - 20 of 25 results