a b s t r a c tA validated high performance thin-layer chromatography (HPTLC) method was developed for simultaneous determination of ursolic acid (UA) and oleanolic acid (OA) contents in Plantago major which were collected from several plantation areas in Indonesia. The cytotoxic effect against two cancer cell lines, SiHa and Hep G2, and antioxidant activity were evaluated using the MTT and DPPH-radical scavenging assay, respectively. The test samples included various extracts of P. major from different plant parts using methanol and water as extracting solvents and pure compounds derived from this plant. The results showed that both plant parts and extracting solvents affected the chemical contents and their biological activities. The contents of UA and OA varied according to the organs and provenances of plant. The highest content of UA (0.22-0.48% dry weight) and OA (0.17-0.33% dry weight) were found in the methanol extract of seed. This extract also exhibited the highest cytotoxic activity (IC 50 value: 174.42-246.38 g/ml), whereas the strongest free radical scavenging activity was obtained from the leaf methanol extract (IC 50 value: 263.57 g/ml). The developed HPTLC method can be used for routine analysis and standardization of P. major crude drugs, extracts, and/or finished products using UA and OA as appropriate markers for anticancer products.

Cervical cancer is one of the most commonly diagnosed cancers in woman worldwide and is the first leading cause of cancer-related deaths in Thai women.1) The major cause of mortality associated with this disease is the metastasis of cancer cells that fails to respond to chemotherapeutic drugs. 2)Novel preventive and therapeutic strategies are therefore urgently needed to decrease the mortality associated with this malignancy.Natural products have been found to be a potential source of novel anticancer drugs over the decades and have much contributed to cancer chemotherapy such as etoposide, camptothecin, paclitaxel, etc. 3) In addition, these chemotherapeutic agents have been reported to exert their antitumor effects by inducing apoptosis. 4) Thus, chemical agents with strong apoptosis-inducing activity but minimal toxicity would be expected to have a potential utility as anticancer drugs.Rhinacanthone (3,4-dihydro-3,3-dimethyl-2H-naphthol-[1,2-b]pyran-5,6-dione), one of the main bioactive naphthoquinones, was isolated from Rhinacanthus nasutus which traditionally used in Thai folk medicine for treating various cancers including cervical and hepatocellular cancers. It has also been reported to have antiproliferative activity in various cancer cells 5,6) and antitumor activity against Dalton's lymphoma in mice.7) It has chemical structure closely related to b -lapachone (3,4-dihydro-2,2-dimethyl-2H-naphthol[1,2-b]pyran-5,6-dione) which was proved to be a novel anticancer drug and DNA topoisomerase I and II inhibitor. 8-11)Recently, we reported that rhinacanthins (C, N and Q), another naphthoquinones isolated from the Rhinacanthus plant, exhibited antiproliferative activity in various cancer cells 5) and induced apoptosis in human cervical carcinoma (HeLaS3) cells involving in G 2 /M cell cycle arrest and activation of caspase-3. 12) Rhinacanthins-N and -Q also act as topoisomerase II inhibitors.13) Therefore, it is possible that rhinacanthone functions on cancer cells by the same action as b-lapachone and/or rhinacanthins. Up to present, the potential anticancer mechanism(s) of this drug has not been elucidated. In present study, effects of rhinacanthone on the induction of apoptosis and its molecular mechanism in human cervical carcinoma (HeLa) cells were investigated. Here, we demonstrate that rhinacanthone, 1,2-naphthoquinone, induces apoptosis on human cervical carcinoma cells. To the best of our knowledge, this is the first report showing that rhinacanthone-induced apoptotic cell death is mediated via mitochondria-dependent pathway. Rhinacanthone would be a candidate for apoptosis-inducing cancer Rhinacanthone, a main bioactive naphthoquinone, isolated from roots of Rhinacanthus nasutus KURZ, (family Acanthaceae), a Thai traditional medicine, has been reported to possess anticancer effects, although the anticancer mechanism is still unclear. Therefore, we investigated the effects of rhinacanthone on cell proliferation, cell cycle progression and apoptosis induction in human cervical carcinoma ( The apoptot...

Background:Plantago major has been reported to have anticancer and anti-inflammatory properties. However, its antiproliferative and anti-inflammatory mechanisms have not been fully elucidated. Moreover, which plant parts are more suitable as starting materials has not been explored.Objectives:To investigate the antiproliferative activity of P. major extracts against MCF-7, MDA-MB-231, HeLaS3, A549, and KB cancer cell lines as well as their effects on inflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-1β, IL-6, and interferon [IFN]-γ) production by lipopolysaccharide (LPS)-stimulated THP-1 macrophages.Materials and Methods:The methanol and aqueous extracts of P. major from different plant parts and its chemical compounds, i.e., ursolic acid (UA), oleanolic acid (OA), and aucubin were tested in this experiment.Results:Methanol and aqueous extracts of P. major seeds exhibited the greatest antiproliferative activity. The methanol extracts of seeds also demonstrated the highest inhibition of TNF-α, IL-1β, IL-6, and IFN-γ production. Interestingly, the roots, which were commonly discarded, exhibited comparable activities to those of leaves and petioles. Furthermore, UA exhibited stronger activities than OA and aucubin.Conclusions:The seeds are being proposed as the main source for further development of anticancer and anti-inflammatory products, whereas the roots could be included in the preparation of P. major derived products with respect to anti-inflammatory.SUMMARY Amongst the parts of Plantago major, seeds exhibited the greatest antiproliferative activity against MCF-7, MDA-MB-231, HeLaS3, A549, and KB cell lines as well as the highest inhibition on TNF-α, IL-1β, IL-6, and IFN-γ productionThe roots, which were commonly discarded, exhibited comparable antiproliferative and cytokines inhibition activities to those of leaves and petiolesUrsolic acid, a chemical compound of Plantago major, exhibited stronger activities than oleanolic acid and aucubinThe seeds are being proposed as the main source for further development of anticancer and anti inflammatory products, whereas the roots could be included in the preparation of Plantago major derived products with respect to anti inflammatory. Abbreviations used: TNF: Tumor Necrosis Factor; IL: Interleukin; IFN: Interferon; HPTLC: High Performance Thin Layer Chromatography; UA: Ursolic Acid; OA: Oleanolic Acid; AUC: Aucubin.

Thirteen cardenolide glycosides (1-13) were isolated from the CHCl and MeOH extracts of Vallaris glabra leaves. The structures of the new compounds (2-13) were identified by spectroscopic methods, with the absolute configurations of the sugar moieties determined by acid hydrolysis. All compounds were evaluated for their cytotoxic activity against human cervix adenocarcinoma, lung carcinoma, and colorectal adenocarcinoma cell lines. The two most potent compounds [2'-O-acetylacoschimperoside P (1) and oleandrigenin-3-O-α-l-2'-O-acetylvallaropyranoside (2)] exhibited IC values in the range of 0.03-0.07 μM.