Glochidone

Growth inhibition of human gynecologic and colon cancer cells by Phyllanthus watsonii through apoptosis induction.[Pubmed:22536331]

PLoS One. 2012;7(4):e34793.

Phyllanthus watsonii Airy Shaw is an endemic plant found in Peninsular Malaysia. Although there are numerous reports on the anti cancer properties of other Phyllanthus species, published information on the cytotoxicity of P. watsonii are very limited. The present study was carried out with bioassay-guided fractionation approach to evaluate the cytotoxicity and apoptosis induction capability of the P. watsonii extracts and fractions on human gynecologic (SKOV-3 and Ca Ski) and colon (HT-29) cancer cells. P. watsonii extracts exhibited strong cytotoxicity on all the cancer cells studied with IC(50) values of PW-10). PW-4-->PW-8 portrayed stronger cytotoxic activity and was further subjected to bioassay-guided fractionation and resulted with 8 sub-fractions (PPWH-1-->PPWH-8). PPWH-7 possessed greatest cytotoxicity (IC(50) values ranged from 0.66-0.83 microg/mL) and was selective on the cancer cells studied. LC-MS/MS analysis of PPWH-7 revealed the presence of ellagic acid, geranic acid, Glochidone, betulin, phyllanthin and sterol glucoside. Marked morphological changes, ladder-like appearance of DNA and increment in caspase-3 activity indicating apoptosis were clearly observed in both human gynecologic and colon cancer cells treated with P. watsonii especially with PPWH-7. The study also indicated that P. watsonii extracts arrested cell cycle at different growth phases in SKOV-3, Ca Ski and HT-29 cells. Cytotoxic and apoptotic potential of the endemic P. watsonii was investigated for the first time by bioassay-guided approach. These results demonstrated that P. watsonii selectively inhibits the growth of SKOV-3, Ca Ski and HT-29 cells through apoptosis induction and cell cycle modulation. Hence, P. watsonii has the potential to be further exploited for the discovery and development of new anti cancer drugs.

Protocols for in vitro culture and phytochemical analysis of Phyllanthus species (euphorbiaceae).[Pubmed:19521844]

Methods Mol Biol. 2009;547:167-77.

We developed reproducible protocols for micropropagation, callus culture, and root culture of the medicinal plant Phyllanthus urinaria, P. niruri, P. tenellus, P. corcovadensis, P. caroliniensis, P. stipulatus, and P. fraternus by using single node explants. Genotype-linked differences are visible among the Phyllanthus species concerning shoot culture, callus culture, and root culture growth. The protocols developed for phytochemical screening of callus and root extracts of P. urinaria, P. caroliniensis, P. stipulatus, and P. fraternus have shown the production of sterols and triterpenes. Both compounds are known to account for the antinociceptive activity of the methanolic extracts as Glochidone and stigmasterol have strong activity against neurogenic and inflammatory pain. Similarly, methanolic callus extracts of P. tenellus, P. niruri and P. corcovadensis have potent analgesic properties, however phenolics are major compounds isolated from these species. The optimized micropropagation, callus culture, and root culture protocols offer the possibility to use cell/root culture techniques for vegetative propagation and secondary metabolite studies.

New triterpenoid saponins from Glochidion eriocarpum and their cytotoxic activity.[Pubmed:19122328]

Chem Pharm Bull (Tokyo). 2009 Jan;57(1):102-5.

Combined chromatographic methods led to the isolation of two new triterpenoid saponins, glochieriosides A and B (1, 2), from the aerial parts of Glochidion eriocarpum, along with three known triterpenes, Glochidone (3), lup-20(29)-en-3beta,23-diol (4), and lup-20(29)-en-1beta,3beta-diol (5). The structures of the new saponins were determined to be 22beta-benzoyloxy-3beta,16beta,28-trihydroxyolean-12-ene 3-O-[beta-D-glucopyranosyl-(1-->3)-alpha-L-arabinopyranoside] (1) and 22beta-benzoyloxy-3beta,16beta,28-trihydroxyolean-12-ene 3-O-[beta-D-glucopyranosyl-(1-->3)-beta-D-xylopyranoside] (2). The structural elucidation was accomplished by using a combination of the 1D-NMR (1H-, 13C-NMR, distortionless enhancement by polarization transfer (DEPT) 90 degrees , and DEPT 135 degrees ), 2D-NMR (1H-1H correlation spectroscopy, heteronuclear multiple quantum correlation, heteronuclear multiple bond correlation, and rotating frame Overhouser effect spectroscopy), ESI-MS, and HR-FAB-MS experiments. Glochieriosides A and B exhibited significant cytotoxic activity against HL-60, HT-29, MCF-7 and SK-OV-3 human cancer cell lines with the IC50 values of 5.5, 6.8, 29.1, and 22.7 microM for glochierioside A, respectively, and 6.6, 18.6, 36.1, and 16.0 microM for glochierioside B. Glochidone was less active with IC50 values greater than 100 microM while lup-20(29)-en-1beta,3beta-diol was moderately active with IC50 values of 43.3, 67.0, 66.1, and 48.0 microM, respectively.

Cytotoxic arylnaphthalide lignan glycosides from the aerial parts of Phyllanthus taxodiifolius.[Pubmed:16450297]

Planta Med. 2006 Jan;72(1):60-2.

The arylnaphthalide lignan glycosides, taxodiifoloside, cleistanthoside A, cleistanthin A and cleistanthin A methyl ether, together with a triterpene, Glochidone, have been isolated from the aerial parts of Phyllanthus taxodiifolius. The structures were established using spectral and chemical methods. Compounds and, as well as the derivatives and exhibited potent cytotoxic activities with GI50 values in the range of 10(-7)-10(-9) M in five cultured mammalian cancer cell lines while the new compound showed moderate activity (GI50 in the order of 10(-6) M). Compounds and were inactive in all tested cell lines.

Activity of lupane triterpenoids from Maytenus species as inhibitors of nitric oxide and prostaglandin E2.[Pubmed:16337130]

Bioorg Med Chem. 2006 Mar 1;14(5):1573-9.

In the present study, we report that three new lupane triterpenes (1-3), in addition to 16 known ones (4-19), were isolated from the root bark of Maytenus cuzcoina and the leaves of Maytenus chiapensis. Their structures were elucidated by spectral analysis, including homonuclear and heteronuclear correlation NMR experiments (COSY, ROESY, HSQC, and HMBC). The natural compounds and derivatives 6a, 6b, 9a, and 9b have been tested for potential anti-inflammatory activity, and several compounds including 3-epicalenduladiol (2), 11alpha-hydroxy-Glochidone (3), rigidenol (6), acetoxy-rigidenol (6a), 11alpha-acetoxy-30-chloro-3-oxo-lup-20(29)-ene (6b), betulin (9), 28-acetoxy-betulin (9a), epibetulin (12), epibetulinic acid (13), and betulonic acid (16) exhibited potent inhibitory effects on NO and prostaglandin E(2) production in mouse macrophages (RAW 264.7) stimulated with bacterial endotoxin. The structure-activity relationship is discussed in detail.

Cytotoxic activity of lupane-type triterpenes from Glochidion sphaerogynum and Glochidion eriocarpum two of which induce apoptosis.[Pubmed:15770539]

Planta Med. 2005 Mar;71(3):208-13.

Six known lupanes lupenone ( 1), 3- epi-lupeol ( 2), Glochidone ( 4), glochidonol ( 5), glochidiol ( 6) and lup-20(29)-ene-1beta,3beta-diol ( 7) were isolated from the roots and stem wood of Glochidion eriocarpum and three, 5, 6 and lup-20(29)ene-3alpha,23-diol ( 3), were isolated from the roots and stem wood of Glochidion sphaerogynum. Compounds were identified by (1)H- and (13)C-NMR techniques. Triterpenes 2 - 7 were tested against the growth of three human tumor cell lines, MCF-7, NCI-H-460 and SF-268. Lupanes 3, 5, and 6 exhibited strong inhibitory effects against all three; thus GI (50) values for 3 were 12.7 +/- 3.7, 17.9 +/- 1.1 and 17.9 +/- 0.5, for 5 9.0 +/- 3.7, 4.9 +/- 0.2 and 9.8 +/- 0.5, and for 6 6.63 +/- 0.7, 7.5 +/- 0.5 and 9.7 +/- 0.3.3. Epilupeol was less active, with GI (50) values of 75.6 +/- 11.7, 86.1 +/- 12.4 and 80.9 +/- 2.6 while 7 was moderately active only against MCF-7 (GI (50) = 79.2 +/- 2.4). Additional studies indicated that triterpenes 5 and 6 exerted their antiproliferative activity through the involvement of apoptosis while triterpene 3 did not.

Potential anti-tumor promoting activity of lupane-type triterpenoids from the stem bark of Glochidion zeylanicum and Phyllanthus flexuosus.[Pubmed:15643564]

Planta Med. 2004 Dec;70(12):1234-6.

Four known lupane-type triterpenoids, glochidonol (1), glochidiol (2), lup-20(29)-ene-1beta,3beta-diol (3) and Glochidone (3) were isolated from the stem bark of Glochidion zeylanicum. Previously, lupeol (5), lup-20(29)-ene-3beta,24-diol (6) and betulin (7) were isolated from the stem bark of Phyllanthus flexuosus. This study reports the assays of these lupane-type triterpenoids: all isolates 1-7 and synthetic analogues, glochidonyl acetate (1a), lup-20(29)-ene-1,3-dione (1b) and lup-20(29)-ene 3beta,24-diacetate (6a) were tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol 13-acetate (TPA). Among them, the effects of compounds 2 (IC50 = 290 mol ratio/32 pmol TPA) and 3 (IC50 = 300) were stronger than the others. In addition, compound 2 exhibited a strong inhibitory effect on mouse skin tumor promotion in an in vivo mouse two-stage carcinogenesis test.

[Studies on chemical constituents of Clerodendrum bungei].[Pubmed:15615412]

Zhongguo Zhong Yao Za Zhi. 2003 Nov;28(11):1042-4.

OBJECTIVE: To study the constituents from Clerodendrum bungei. METHOD: The constituents were isolated and purified with chromatographic methods, and identified by NMR, MS and IR. RESULT: Five compounds were isolated, beta-sitosterol (1), taraxerol (2), Glochidone (3), glochidonol (4), glochidiol (5). CONCLUSION: Compounds (3), (4) and (5) were isolated for the first time from C. bungei.

Pharmacological activity and chemical composition of callus culture extracts from selected species of Phyllanthus.[Pubmed:11189874]

Pharmazie. 2000 Dec;55(12):945-6.

This study was conducted in order to determine the chemical composition and the possible antinociceptive effects in mice of some species of Phyllanthus in vitro. The methanolic extracts obtained from callus cultures of P. fraternus, P. stipulatus and P. caroliniensis caused significant inhibition in to the late phase of the formalin test, whereas the extract from P. urinaria inhibited both neurogenic and inflammatory phases of the test. Conventional chromatographic methods (TLC, GC) permitted the detection of some steroids or triterpenes, including beta-sitosterol, glochidonol and Glochidone, which seem be responsible for the antinociceptive effects of the callus extracts studied.

Isolation and identification of compounds with antinociceptive action from Ipomoea pes-caprae (L.) R. Br.[Pubmed:10399194]

Pharmazie. 1999 Jun;54(6):464-6.

This study describes the isolation and identification of several constituents from Ipomoea pes-caprae (L.) R. Br., a medicinal plant frequently employed in folk medicine of many countries as a remedy against several diseases, including inflammation and pain. Our results demonstrate that some of these compounds, such as Glochidone, betulinic acid, alpha- and beta-amyrin acetate, isoquercitrin, etc. showed pronounced antinociceptive properties in the writhing test and formalin test in mice. These data confirm our previous work concerning the antinociceptive action of the hydroalcoholic extract of I. pes-caprae and justify, at least in part, the popular use of this plant for the treatment of dolorous processes.