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Anticancer activities of Oldenlandia diffusa.
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James Offline
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Anticancer activities of Oldenlandia diffusa.
J Herb Pharmacother. 2004;4(1):21-33.

Anticancer activities of Oldenlandia diffusa.

Gupta S, Zhang D, Yi J, Shao J.

Source

Department of Pharmacy & Administrative Sciences, College of Pharmacy & Allied Health Professions, St. John's University, Jamaica, NY., USA.

Abstract

OBJECTIVES:

To investigate the anticancer activities of a Chinese herb, Oldenlandia diffusa (Bai Hua She She Cao).

METHODS:

The water extract of the raw herb Oldenlandia diffusa was used in this study. The in vitro anti-proliferative activities of the extract were tested against eight cancer cell lines and one normal cell line. Microscopic examination and DNA ladder analysis were carried out to determine the pro-apoptotic effect of the extract. In vivo studies were carried out to examine the anticancer activities of the extract using C57BL/6j mice bearing B16-F10 lung metastasis. Oldenlandia diffusa extract was given at the dose level of 5 g raw material/kg on Days 3-12 by oral gavage and the extent of lung metastases were examined on Day 14.

RESULTS:

The extract exhibited a strong antiproliferative activity against all cancer cell lines tested. The concentrations of growth inhibition at 50% (IC(50)) ranged from 7 to 25 mg raw material/ml after 48-hour treatment. The extract had a very limited cytotoxicity (10% inhibition) on the normal pancreatic cells even at the concentration of 50 mg/mL. Apoptosis in B16-F10 cells after treatment with the extract was observed by microscopic examination and DNA ladder assays. Oral administration of the herbal extract effectively reduced B16-F10 cell growth in the lungs of C57Bl/j mice with a 70% reduction in lung metastases (p < 0.001).

CONCLUSIONS:

Oldenlandia diffusa extract effectively inhibited the growth of all the eight cancer cell lines and induced significant increase of apoptosis. The extract exhibited minimum toxic effect on normal pancreatic cells. Furthermore, there was a significant inhibition of lung metastases in the animal model with no noticeable adverse effects. The herb extract could be a potential anticancer agent.

http://www.MountainMistBotanicals.com
(This post was last modified: 02-11-2013 12:15 AM by James.)
02-11-2013 12:04 AM
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James Offline
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Evidence for Oldenlandia diffusa-evoked cancer cell apoptosis
Zhong Xi Yi Jie He Xue Bao. 2006 Sep;4(5):485-9.

Evidence for Oldenlandia diffusa-evoked cancer cell apoptosis through superoxide burst and caspase activation.

Yadav SK, Lee SC.

Source

Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117597.

Abstract

BACKGROUND & OBJECTIVE:

Oldenlandia diffusa (Bai Hua She She Cao) is one of the herbs most commonly used in traditional Chinese medicine for treating cancer. Various studies using the herb alone or in combination with other therapy plans have evidenced the effectiveness of the herb in the management of cancers of different tissue origin. However, the mechanisms underlying its anti-cancer activity are unknown. In the present study, we attempted to investigate the apoptotic activity of crude extracts of the herb as well as the possible molecular pathways.

METHODS:

We incubated human promyelocytic leukemia cell line HL60 cells with ethanol or aqueous extracts of the herb, and determined the levels of intracellular superoxide at 2 and 4 hours as well as caspase activity at 3, 6 and 8 hours using photospectrometry. Cancer cell survival and apoptosis were quantified at 24 hours by using MTT and flow cytometry analyses respectively.

RESULTS:

We found that it dose-dependently inhibited the cancer cell growth in MTT assay. Flow cytometry analysis revealed that it elicited significant production of sub-G(1) population of the cells, indicating the extract-evoked cell apoptotic death. The LD(50) of the ethanol extract was estimated to be approximately 320 microg/ml. Moreover, treatment of the cancer cells with the ethanol component markedly increased the production of superoxide within few hours. Significant elevation in the protease activities of caspases-2 and -3 were detected at as early as 3 and 6 hours respectively.

CONCLUSION:

Our results show that the ethanol extract of the herb effectively evokes cancer cell apoptosis, possibly through burst-mediated caspase activation.

http://www.MountainMistBotanicals.com
(This post was last modified: 02-11-2013 12:14 AM by James.)
02-11-2013 12:05 AM
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James Offline
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Apoptotic effect of Oldenlandia diffusa on the leukaemic cell line HL60
J Ethnopharmacol. 2007 Dec 3;114(3):290-9. Epub 2007 Aug 19.

Apoptotic effect of Oldenlandia diffusa on the leukaemic cell line HL60 and human lymphocytes.

Willimott S, Barker J, Jones LA, Opara EI.

Source

School of Life Sciences, Kingston University, Penryhn Road, Kingston upon Thames, Surrey KT1 2EE, UK.

Abstract

Oldenlandia diffusa is traditionally prescribed in the treatment of a number of cancers and studies suggest that it exerts a cytotoxic action specific to cancer cells. To further investigate this suggested action, the effect(s) of Oldenlandia diffusa on leukaemic cells (HL60) and stimulated and unstimulated human blood lymphocytes (PBLs) was investigated. For the HL60s, cell growth, apoptotic induction, alterations in cell cycle characteristics and genotoxicity were investigated. For the PBLs, apoptotic induction and alterations in cell cycle characteristics were investigated. Preliminary chemical analysis to identify the cytotoxic constituents of Oldenlandia diffusa was also carried out. Results showed that Oldenlandia diffusa significantly inhibited the growth of the HL60s and induced apoptosis in a cell cycle-independent fashion, possibly through the induction of genotoxic damage. Oldenlandia diffusa did not induce apoptosis in the PBLs however progression through the cell cycle was not evident (in stimulated PBLs) suggesting some degree of cytotoxicity. Preliminary chemical analysis indicated that a number of compounds appear to be responsible for the cytotoxic action of Oldenlandia diffusa. These results indicate that HL60s are more sensitive to Oldenlandia diffusa than stimulated PBLs and thus support a cytotoxic action for Oldenlandia diffusa that has some degree of specificity.

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(This post was last modified: 02-11-2013 12:14 AM by James.)
02-11-2013 12:08 AM
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Cytotoxicity and bioavailability studies on a decoction of Oldenlandia diffusa
J Ethnopharmacol. 2010 Sep 15;131(2):396-403.

Cytotoxicity and bioavailability studies on a decoction of Oldenlandia diffusa and its fractions separated by HPLC.

Ganbold M, Barker J, Ma R, Jones L, Carew M.

Source

School of Pharmacy & Chemistry, Kingston University, Kingston upon Thames, Surrey, UK.

Abstract

AIM OF THE STUDY:

Oldenlandia diffusa is a traditional Chinese herbal remedy with known cytotoxic activity in vitro and in vivo. The aim of the study was to identify the most cytotoxic constituents of a water extract (a decoction is traditionally used as a treatment) by HPLC and activity-guided fractionation. The bioavailability of the decoction and certain fractions, and the mode of cell death induced by these mixtures, were also investigated.

MATERIALS AND METHODS:

A decoction of O. diffusa was prepared and separated by HPLC into eleven fractions (F1-11) for testing on the growth of HL60 leukaemia cells; two of the most active fractions were also tested on Caco-2 colon cancer cells. Cell viability was measured by trypan blue exclusion, DNA content (Cyquant NF assay) and neutral red uptake. Evidence of apoptosis was gained from cells stained with the nuclear dye DAPI, and detection of cleaved poly (ADP-ribose) polymerase (PARP) by Western blot.

RESULTS:

Fraction 9 was found to be the most active fraction, and, along with the decoction, induced apoptosis. Cells stained with DAPI showed a decrease in cell size and nuclear fragmentation characteristic of apoptosis. Detection of cleaved PARP further confirmed induction of apoptosis by O. diffusa decoction and fraction 9. The bioavailability of O. diffusa was investigated by production of post-absorption samples using Caco-2 intestinal epithelial monolayers. Addition of post-absorption samples (taken from the basolateral side after 3h incubation with the decoction on the apical side) inhibited the growth of HL60 cells, and suggested a degree of bioavailability. The constituents in fraction 9 were further separated by HPLC and eight major compounds were identified by LC-MS: two of these were ursolic acid (UA) and its enantiomer oleanolic acid (OA). Concentrations of UA and OA in the decoction were then calculated by reference to the area of the peaks of UA and OA found in F9. The post-absorption sample of F9 contained six of the eight constituents in the original pre-absorption fraction 9.

CONCLUSIONS:

Taken together, the results suggest that certain constituents, possibly including ursolic/oleanolic acid, may be bioavailable and at sufficient concentration to induce apoptosis in cancer cells in vitro through a mechanism including the cleavage of PARP.

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(This post was last modified: 02-11-2013 12:13 AM by James.)
02-11-2013 12:10 AM
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Oleanolic acid isolated from Oldenlandia diffusa exhibits a unique growth inhibitory
Life Sci. 2009 Jul 17;85(3-4):113-21. doi: 10.1016/j.lfs.2009.04.025. Epub 2009 May 9.

Oleanolic acid isolated from Oldenlandia diffusa exhibits a unique growth inhibitory effect against ras-transformed fibroblasts.

Wu PK, Chi Shing Tai W, Liang ZT, Zhao ZZ, Hsiao WL.

Source

School of Chinese Medicine, 7 Baptist University Road, Hong Kong Baptist University, Kowloon Tong, Hong Kong.

Abstract

AIMS:

Oldenlandia diffusa (Willd.) Roxb. (O. diffusa) is a commonly used traditional Chinese medicine for treating cancer. Its pharmacological activities and anti-cancer effects have been the focus of intense research in recent years. In the present study, we aim to investigate whether the five major compounds from O. diffusa possess a unique inhibitory activity against ras-transformed cells in a well-established cell model.

MAIN METHODS:

The anti-cancer effects of O. diffusa were assessed in a co-culture system containing normal and transformed Rat 6 (R6) fibroblasts. In addition, a transwell assay was used to examine the interaction between the drugs and the co-cultivated cells.

KEY FINDINGS:

Our data showed that among the samples tested, oleanolic acid (OA), but not the structural isomer ursolic acid (UA), inhibits the growth of ras oncogene-transformed R6 cells at a dosage that is not toxic to the co-cultivated normal fibroblasts. A significant inhibitory effect was also observed in the transwell experiments, indicating that the mode of action for OA-mediated growth inhibition of transformed cells does not require direct cell-to-cell contact between normal and ras-transformed cells. Data obtained from experiments conducted with the conditioned medium that was collected from normal R6 cells treated with OA also suggest that OA might cause normal cells to secrete inhibitory factor(s) against the transformed cells. The enhanced ability of OA to cause cytotoxicity in transformed cells in the presence of normal fibroblasts is also observed with the human hepatocellular carcinoma cell line, SMMC-7721.

SIGNIFICANCE:

The present study demonstrates that OA may possess both cancer chemotherapeutic and chemopreventive activities. Thus, it may have great potential for clinical application as a novel anti-cancer drug.

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02-11-2013 12:12 AM
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