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Family Meliaceae
Hamboro
Aglaia foveolata Pannell
PITTED AGLAIA

Scientific names Common names
Aglaia foveolata Pannell Hamboro (Fil.)
  Pitted aglaia (Engl.)
Aglaia foveolata Pannell is an accepted name. There are no recorded synonyms. KEW: Plants of the World Online

Other vernacular names
MALAY: Bekak, Memberas.
OTHERS: Fun, Tamasewo, Garanki, Muge, Hamboro, Lantupah, Lantupak, Layma mindi, Ndabuk, Ndraut, Penarahan putay, Koping-koping nusa, Putih, Rangkori, Bahko brawo, Bogosoup, Bunlau, Lepuniau, Enger milomb, Kajoe hase boenga, Kajoe si marbatos-ni-bodat, Milomb neker, Nembasina, Ulukwala, Ulukwalo, Usopalpal, Segera. (These vernacular names were lumped together without clear attribution to specific country or language. This will be updated on a later date.)

Gen info
- Aglaia is a genus of 121 recognized species of woody dioecious 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).

Botany
• 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)

Distribution
- Native to the Philippines.
- Also native to in Borneo, Malaya, Sumatera.

- Reported in Mt. Salibbongbong, Panay, Capiz Province and Aurora Province.
- IUCN Red List:Listed as 'Near Threatened', 1998.

Constituents
- 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). (15)
- Study of stem bark isolated four compounds viz., (1) 17,24-epoxy-25-hydroxybaccharan-3-one, (2) β-stigmasterol glucoside, (3) Eichlerianic acid, and (4) 17,24-epoxy-25 -hydroxy-3- oxobaccharan-21-oic acid, which is a class of triterpenoid and steroid compounds. (see study below) (19)
- Study (21)

Properties
- Aglaia species are known to have various biologic activities viz. anticancer, anti-inflammatory, antioxidant, antidiabetic, and nanoparticle activity.
- Studies have suggested anticancer, antiviral, antioxidant, antibacterial, antibiofilm properties.

Parts used
Fruit, leaves, twigs.

Uses

Edibility
- Fruit is edible with a sweet flavor.
Folkloric
- No reported folkloric medicinal use in the Philippines.

Studies
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)
Silvestrol / 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-virus 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)
Silvestrol 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)
Antioxidant / Antibacterial / Cytotoxic / Stem Bark: Study isolated the active compound from stem bark of A. foveolata and evaluated its antioxidant, cytotoxic, and antibacterial activities. Four compounds were isolated viz., (1) 17,24-epoxy-25-hydroxybaccharan-3-one, (2) β-stigmasterol glucoside, (3) Eichlerianic acid, and (4) 17,24-epoxy-25 -hydroxy-3- oxobaccharan-21-oic acid, which is a class of triterpenoid and steroid compounds. Compound 3 showed best antioxidant activity using ABTS method. Compound 4 showed cytotoxic activity against MCF-7 cancer cells by MTT method. Compounds 1 2, and 4 showed showed antibacterial activity against E. coli, S. aureus, and B. subtilis, while compound 3 showed activity against P. aeruginosa. (19)
Antioxidant, Antibacterial, Antibiofilm Activities / Endophytic Fungi / Leaves: Study isolated two endophytic fungi from A. foveolata leaves, which were identified phenotypically and genotypically as Penicillium sp. SAF6-EGY strain AFL.2 and Arthrinium sp. R22-1 strain AFL.3. The EA extract of AFL.2 and AFL.3 showed relatively similar total phenolic content (TPC) and total flavonoid content (TFC). AFL3 showed showed highest antioxidant activity in DPPH, ABTS assays with IC50s of 123.41 and 256.95 µg/mL respectively. AFL2 showed strongest antibacterial activity against E. coli and S. aureus with same MICs of 250 µg/mL. AFL.2 showed best antibiofilm activity against E. coli, while AFL.3 against B. subtilis biofilm with inhibition value of 42 and 35% respectively. LC-MS/MS revealed both AFL.2 and AFL.3 extract contained putative antibacterial compounds corresponding to its promising activity. (20)

Availability
- Wild-crafted.


Updated October 2024
March 2020

PHOTOS / ILLUSTRATIONS
IMAGE SOURCE: Aglaia foveolata / Leaf / Aurora Province, slopes of Mt. Mingan, Luzon, Philippines / © 2015: P B Pelser & J F Barcelona / Contact: pieter.pelser@canterbury.ac.az / ref: DOL95181 / Phytoimages.siu.edu
OTHER IMAGE SOURCE: Aglaia foveolata / Infructescence / Aurora Province, slopes of Mt. Mingan, Luzon, Philippines / © 2015: P B Pelser & J F Barcelona / Contact: pieter.pelser@canterbury.ac.az / ref: DOL95184 / Phytoimages.siu.edu
OTHER IMAGE SOURCE: Aglaia foveolata / Abaxial view of leaflet / © 2015: P B Pelser & J F Barcelona / Contact: pieter.pelser@canterbury.ac.az (ref.DOL95157) / Phytoimages.siu.edu
OTHER IMAGE SOURCE: Aglaia foveolata / Leaflet / © 2015: P B Pelser & J F Barcelona / Contact: pieter.pelser@canterbury.ac.az (ref.DOL95132) / Phytoimages.siu.edu

Additional Sources and Suggested Readings
(1)
Aglaia foveolata Pannell / KEW: Plants of the World Online

(2)
Silvestrol, a potential anticancer rocaglate derivative from Aglaia foveolata, induces apoptosis in LNCaP cells through the mitochondrial/apoptosome pathway without activation of executioner caspase-3 or -7. / Kim S, Hwang BY, Su BN, Chai H, Mi Q, Kinghorn AD, Wild R, Swanson SM / Anticancer Res. 2007 Jul-Aug; 27(4B): pp 2175-2183 / PMID: 17695501  / PMCID: PMC2787233
(3)
Constituents of the Leaves and Stem Bark of Aglaia foveolata / Angela A. Salim, Hee-Byung Chai, A. Douglas Kinghorn et al / Tetrahedron, 2007; 63(33): pp 7926-7934/ DOI: 10.1016/j.tet.2007.05.074 / PMID: 18698338 PMCID: PMC2034361
(4)
Silvestrol, a Rocaglate Derivative from the Indonesian Plant Aglaia foveolata, Has Significant Bcl-2- and p53-Independent Anti-Tumor Activity against Chronic Lymphocytic Leukemia Cells. / Ryan B. Edwards, BS; David M. Lucas, PhD; Gerard Lozanski, MD; Amy J. Johnson, PhD; Bao-Ning Su, PhD; Thomas S. Lin, MD; John C. Byrd, MD; A. Douglas Kinghorn, PhD; A. Douglas Kinghorn, PhD / Blood, Nov 2006; 108(11) / https://doi.org/10.1182/blood.V108.11.2600.2600
(5)
Silvestrol induces early autophagy and apoptosis in human melanoma cells / Wei-Lun Chen, Li Pan, A Douglas Kinghorn, Steven M Swanson, Joanna E Burdette / BMC Cancer, 2016; 16(Art17)
(6)
Aglaia foveolata / Ken Fern: Tropical Plants Database / Useful Tropical Plants
(7)
Therapeutic Potential of the Translation Inhibitor Silvestrol in Hepatocellular Cancer / Takayuki Kogure, A. Douglas Kinghorn, Irene Yan, Brad Bolon, David M. Lucas, Michael R. Grever, Tushar Patel  / PLOS ONE / https://doi.org/10.1371/journal.pone.0076136
(8)
In the News: Leukaemia inhibitor from tree extract can help fight cancer / The Star
(9)
Aglaia foveolata / IUCN Red List
(10)
The natural compound silvestrol inhibits hepatitis E virus (HEV) replication in vitro and in vivo / Daniel Todta, Nora Moeller, Dimas Praditya, Volker Kinast, Martina Friesland, Michael Engelmann, Lieven Verhoye, Ibrahim M. Sayed, Patrick Behrendt, Viet Loan Dao Thi, Philip Meuleman, Eike Steinmann / Antiviral Research, 2018; 157: pp 151-158
(11)
In the News: Compound from Tropical Plant Targets Key Cancer-Causing Genes / Julie Grisham / Memorial Sloan Kettering Cancer Center
(12)
Isolation and Characterization of Minor Analogues of Silvestrol and Other Constituents from a Large-Scale Re-collection of Aglaia foveolata / Li Pan, Leonardus B S Kardono, Soedarsono Riswan, Heebyung Chai, Esperanza J Carcache de Blanco et al / J. Nat. Prod. 2010 73(11): pp 1873-1878 / https://doi.org/10.1021/np100503q
(13)
The Natural Compound Silvestrol Is a Potent Inhibitor of Ebola Virus Replication / Nadine Biedenkopf, Kerslin Lange Grunweller et al / Antiviral Res., Jan 2017; 137: pp 76-81 / PMID: 27864075 / DOI: 10.1016/j.antiviral.2016.11.011
(14)
Inhibition of Zika Virus Replication by Silvestrol / Fabian Elgner, Catarina Sabino, Eberhard Hildt et al / Viruses 2018; 10(4) /  doi: 10.3390/v10040149 / PMCID: PMC5923443 / PMID: 29584632
(15)
Silvestrol 5”’, 6”’-diacetate, a semi-synthetic rocaglate derivative from the Indonesian plant Aglaia foveolata, has anti-tumor activity against Chronic Lymphocytic Leukemia cells in vitro / David M. Lucas Ryan B. EdwardsBao-Ning SuThomas LinJohn C. ByrdA. Douglas Kinghorn and Michael R. Grever / Proc Amer Assoc Cancer Res, 2006, Vol 47
(16)
Molecular mechanisms and anti‐cancer aspects of the medicinal phytochemicals rocaglamides (=flavaglines) / Min Li-Weber / IJC: International Journal of Cancer, Oct 2015; 137(8): pp 1791-1799
(17)
An Overview on the Biological Perspectives of Aglaia Species / Priya R Sowmiya P, Meenakshi Sundaram Muthuraman / Asian Journal of Pharmaceutical and Clinical Research, 2018; 11(9) / DOI: 10.22159/ajpcr.2018.v11i9.26436
(18)
Aglaia / Wikipedia
(19)
Isolation and activity test of antioxidant, antibacterial, and cytotoxic compounds from the stem bark of Aglaia foveolata Pannell / Anselma Kartini Dhey, Eka Rasuna Andriani, Chairil Anwar, Winarto Haryadi et al / Pharmacia, 2023; 70(4): pp 1329-1334 / DOI: 10.3897/pharmacia.70.e111111
(20)
Antioxidant, Antibacterial and Antibiofilm Activities of an Endophytic Fungi, Penicillium Sp. SAF6-EGY Strain AFL.2 and Arthrinium Sp. R22-1 Strain AFL.3 Isolated from Aglaia Foveolata / Muhammad E Prastya, Jepri A Priyanto, Gian Primahana, Tjandrawati Mozef et al / Proceedings of the 1st International Conference on Health Research - BRIN (ICHR 2022) / DOI: 10.2991/978-94-6463-112-8_32
(21)
The Cytotoxic Activity of Dammarane-Type Triterpenoids Isolated from the Stem Bark of Aglaia cucullata  (Meliaceae) / Purnama, Kindi Farabi, Dudi Runadi, Hadi Kuncoro, Unang Supratman et al / Molecules, 28(13) / DOI: 10.3390/molecules28134946

DOI: It is not uncommon for links on studies/sources to change. Copying and pasting the information on the search window or using the DOI (if available) will often redirect to the new link page. (Citing and Using a (DOI) Digital Object Identifier)

                                                            List of Understudied Philippine Medicinal Plants
                                          New plant names needed
The compilation now numbers over 1,500 medicinal plants. While I believe there are hundreds more that can be added to the collection, they are becoming more difficult to find. If you have a plant to suggest for inclusion, native or introduced, please email the info: scientific name (most helpful), local plant name (if known), any known folkloric medicinal use, and, if possible, a photo. Your help will be greatly appreciated.

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