- Aglaia is a genus of 117 species of woody trees belonging to the Mahogany family (Meliaceae), occurring in the subtropical and tropical forests of Southeast Asia, northern Australia and the Pacific. (18)
- Some species have been placed in the genus Lansium.
- In the Philippines, about 60 Aglaia species
have been reported.
- To date, Aglaia species included in this medicinal plant compilation are Aglaia odorata and A. domestica (Lansium parasiticum).
Aglaia foveolata is an evergreen tree, growing to a height of 20-25 meters, with a dense, feathery crown, bole up to 60 centimeters diameter, with buttresses up to 75 centimeters high and 30 centimeters outwards. Fruits are brown, orange or yellow, subglobose, up to 25 millimeters long, containing 2 seeds covered with a thin, sweet-tasting flesh. (6)
- Found in Southeast Asia - Borneo, Malaysia, Indonesia, Philippines.
- Reported in Mt. Salibbongbong, Panay, Capiz Province and Aurora Province.
- IUCN Red List:Listed as 'Near Threatened', 1998.
- Study of leaves isolated silvestrol (0.002% w/w yield) (1) and five new flavagline derivatives (2-6), along with pyramidatine (7), a biogenetic precursor of flavaglines (foveoglin A, foveoglin B, isofoveoglin, cyclofoveoglin secofoveoglin: 2-6). Silvestrol was also isolated from the stem bark (0.02% w/w) along with new baccharane-type triterpenoid (8). Tested against a panel of cancer cell lines, only compound 2 was cytotoxic (IC50 range 1.4-1.8 µM). (see study below) (2)
- Study of stem bark yielded baccharane-type triterpenoid and silvestrol,17,24-epoxy-25-hydroxy-3-oxobaccharan-21-oic acid and dammarane triterpenes, foveolins A and B, together with three known, 3-epi-ocotillol, eichlerianic acid and shoreic acid. (2)
- Study of a large-scale recollection of the CHCl3-soluble extract of stem bark of A. foveolata isolated two new minor silvestrol analogues 2'''-episilvestrol (1) and 2''',5'''-diepisilvestrol (2), along with a new 21-norbaccharane-type triterpene (3), two new 3,4-secodammarane triterpenes (4 and 5), and a new eudesmane sesquiterpene (6), as well as nine known compounds. (see study below) (12)
- Bioassay-guided fractionation isolated two cytotoxic rocaglate derivatives possessing an unusual dioxanyloxy unit, silvestrol and episilvestrol (1), along with a known compound, rocaglaol (2).
- Aglaia species are known to have various biologic activities viz. anticancer, anti-inflammatory, antioxidant, antidiabetic, and nanoparticle activity.
Studies have suggested anticancer, antiviral properties.
Fruit, leaves, twigs.
- Fruit is edible with a sweet flavor.
- No reported folkloric medicinal use in the Philippines.
• Silvestrol / Anticancer / Apoptosis in Human Prostate Cancer Cell Line / Fruits and Twigs: Study evaluated a novel cyclopenta[b]benzofuran, silvestrol, from fruits and twigs. The compound exhibited potent in vitro cytotoxic activity against several human cancer cell lines.. It was active in vivo P388 murine leukemia model. Study evaluated the mechanism of cytotoxicity medicated by silvestrol in LNCaP (hormone-dependent human prostate cancer) cell line. Results demonstrated the involvement of the apoptosome/mitochondrial pathway and suggest the possibility that silvestrol may also trigger the extrinsic pathway of programmed cell death signaling in tumor cells. (2)
• Cytotoxicity / Leaves and Stem Bark: Study of leaves isolated a previously known potent cytotoxic agent silvestrol (0.002% w/w yield) (1) and five new flavagline derivatives (2-6). Pyramidatine (7), a biogenetic precursor of flavaglines 2-6 was isolated from the leaf extract. Silvestrol was also isolated from the stem bark (0.02% w/w) along with new baccharane-type triterpenoid (8). Tested against a panel of cancer cell lines, only compound 2 was cytotoxic (IC50 range 1.4-1.8 µM). Compound two also showed significant NF-kB inhibitory activity in an Elisa assay (IC50 0.37µM). (see constituents above) (3)
• Anti-tumor Activity / Silvestrol / Chronic Lymphocytic Leukemia Cells: Chronic lymphocytic leukemia (CLL) is an incurable disease with limited therapeutic options. Study isolated silvestrol, a focaglate derivative from A. foveolata. Silvestrol was tested against tumor cells obtained from CLL patients. It exhibited significant activity with LC50 of 10 nM at 72 hours by MTT assay. Results showed silvestrol has efficacy against CLL cells in vitro, with highly unusual B-cell specificity and is independent of key CLL resistance mechanisms. (4)
• Autophagy and Apoptosis / Human Melanoma Cells: Study evaluated whether inhibition of protein synthesis caused by silvestrol triggers autophagy and apoptosis in cultured human cancer cells derived from solid tumors. This study evaluated the mechanism of action of silvestrol in MDA-MB-435 melanoma cells. Results showed silvestrol potently inhibited cell growth and induced cell death in human melanoma cells through induction of early autophagy and caspase-mediated apoptosis. (5)
• Silvestrol / Translation Inhibition / Hepatocellular Cancer: Hepatocellular cancers frequently involve fibrosis and a hepatic regenerative response requiring new cell growth. Treatment options for these cancers have not targeted protein synthesis. Silvestrol a rocaglate from A. foveolata can inhibit protein synthesis by modulating the initiation of translation. This study evaluated the therapeutic efficacy of silvestrol using human HCC in vivo and in vitro. Silvestrol inhibited cell growth with IC50 of 12.5 nM in four different HCC cell lines. In vitro silvestrol increases apoptosis and caspase 3/7 activity with loss of mitochondrial membrane potential and decreased expression of Mcl-1 and Bcl-xL. It also showed a synergistic effect when combined with other therapeutic agents. Results suggest potential for targeting of translation in the treatment of HCC. (7)
• Silvestrol / Inhibition of Hepatitis E Virus Replication Hepatitis E virus (HEV), a member of the genus Orthohepevirus in the family Hepeviridae, is the causative agent of Hepatitis E in humans It can be a cause of both acute and chronic hepatitis. This study evaluated silvestrol, isolated from Aglaia foveolata, known for its specific inhibition of the DEAD-box RNA helicase eIF4S in HEV experimental model systems. Study showed silvestrol can be identified as a pangenotypic HEV replication inhibitor in vitro with additive effect to RBV and also exhibited high potency in vivo. Results suggest a potential treatment strategy for chronic hepatitis E in immunocompromised patients. (10)
• Minor Analogues of Silvestrol / Cytotoxicity / Stem Bark: Study of a large-scale recollection of the CHCl3-soluble extract of stem bark of A. foveolata isolated two new minor silvestrol analogues 2'''-episilvestrol (1) and 2''',5'''-diepisilvestrol (2), along with a new 21-norbaccharane-type triterpene (3), two new 3,4-secodammarane triterpenes (4 and 5), and a new eudesmane sesquiterpene (6), as well as nine known compounds. All the isolates were tested against HT-29 cells. The new silvestrol analogues (1 and 2) were considerably less cytotoxic than silvestrol (7) and episilvestrol (5'''-episilvestrol) (8) against the cell line, showing importance of the C-2''' configuration in mediating such activity. (12)
• Sllvestrol / Potent Inhibitor of Ebola Virus Replication: Silvestrol, a natural compound isolated from A. foveolata is a highly efficient, non-toxic, and specific inhibitor of eIF4A. 5'-capped viral mRNAs often contain structured 5'-UTRs as well, which suggest a dependence on eIF4A for their translation by host protein synthesis machinery. In the Ebola virus (EBOV) outbreak in West Africa, the identification of potent antiviral compounds is urgently needed. Ebola mRNAs are 5'-capped and harbor RNA secondary structures in their extended 5'-UTRs. Study showed silvestrol inhibits EBOV infection at low nanomolar concentrations, correlating with an almost complete disappearance of EBOV proteins. Results suggest silvestrol is a promising first-line drug for treatment of acute EVOV and possible other viral infections. (13)
• Sllvestrol / Inhibition of Zika Virus Replication: The Zika virus (ZIKV) outbreak in 2016 in South America highlighted the need for new antiviral substances with broad-spectrum activities against emerging viral pathogens. Recently, silvestrol isolated from Aglaia foveolata was found to have very potent antiviral effects against (-)-strand RNA-irus Ebola virus as well as against Corona- and Piconaviruses with a (+)-strand RNA-genome. Study evaluated the effects of silvestrol on ZIKV replication in A549 cells and primary human hepatocytes. Silvestrol showed potential for significant inhibition of ZIKV replication for both strains. Study data may contribute to the identification of host factors involved in the control of ZIKV infection and to develop antiviral concepts for the treatment of a variety of viral infections without risk of resistance because of a targeted host protein. (14)
• Sllvestrol 5",6"-Diacetate / Semi-Synthetic Rocaglate Derivative / Anti-Tumor: Bioassay-guided fractionation previously isolated two cytotoxic rocaglate derivatives possessing an unusual dioxanyloxy unit, silvestrol and episilvestrol (1), along with a known compound, rocaglaol (2).The two isolates and some transformation products of silvestrol exhibited potent in vitro cytotoxic activity against some human cancer cell lines. While the mechanism of action is not fully understood, silvestrol was found to induce apoptosis through the mitochondrial/apoptosome pathway in LNCap (hormone-dependent human prostate cancer) cells. This study tested silvestrol 5",6"-diacetate and rocaglaol against tumor cells from eight CLL patients. Results showed significant antitumor activity against CLL cells with estimated LC50 of approximately 125 nM after 72 hours incubation. Rocaglaol showed less potency against CLL cells. Results suggest the diacetate of silvestrol has potential as antitumor agent in CLL. (15)
• Sllvestrol / Inhibition of Protein Synthesis in Cell-Free Translation Systems: Silvestrol, isolated from A. foveolata, was found to inhibit protein synthesis in vitro in several different cell-free translation systems and inhibited mRNA translation by stabilization of RNA-binding of eIF4A in the eIF4F complex. (16)