Bioactive Lignans from Zanthoxylum alatum Roxb. stem bark with cytotoxic potential

Mukhija, Minky; Dhar, K.L.; Kalia, Ajudhia Nath

doi:10.1016/j.jep.2013.12.039

Cited by 30 publications

(19 citation statements)

References 24 publications

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“…A pure compound obtained as colorless crystal, 18 mg; R f 0.39 (toluene: ethyl acetate: formic acid, 6:3.5:0.5); having a melting point 168 °C. Compound gave positive FeCl 3 test for phenolics [39] . UV λmax (methanol): 318 nm, The IR (KBr) cm −1 spectrum showed the absorption band 3436 (—OH str.…”

Section: Resultsmentioning

confidence: 96%

Hepatoprotective potential of antioxidant potent fraction from Urtica dioica Linn. (whole plant) in CCl 4 challenged rats

2015

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The aim of the present study was to isolate hepatoprotective component from Urtica dioica Linn. (whole plant) against CCl4-induced hepatotoxicity in-vitro (HepG2 cells) and in-vivo (rats) model. Antioxidant activity of hydro alcoholic extract and its fractions petroleum ether fraction (PEF), ethyl acetate fraction (EAF), n-butanol fraction (NBF) and aqueous fraction (AF) were determined by DPPH and NO radicals scavenging assay. Fractions were subjected to in-vitro HepG2 cell line study. Further, the most potent fraction (EAF) was subjected to in-vivo hepatoprotective potential against CCl4 challenged rats. The in-vivo hepatoprotective active fraction was chromatographed on silica column to isolate the bioactive constituent(s). Structure elucidation was done by using various spectrophotometric techniques like UV, IR, 1H NMR, 13C NMR and MS spectroscopy. Ethyl acetate fraction (EAF) of hydro-alcoholic extract of U. dioica possessed the potent antioxidant activity viz. DPPH (IC50 78.99 ± 0.17 μg/ml) and NO (IC50101.39 ± 0.30 μg/ml). The in-vitro HepG2 cell line study showed that the EAF prevented the cell damage. The EAF significantly attenuated the increased liver enzymes activities in serum and oxidative parameters in tissue of CCl4-induced rats, suggesting hepatoprotective and anti-oxidant action respectively. Column chromatography of most potent antioxidant fraction (EAF) lead to the isolation of 4-hydroxy-3-methoxy cinnamic acid (ferulic acid) which is responsible for its hepatoprotective potential. Hence, the present study suggests that EAF of hydro-alcoholic extract has significant antioxidant and hepatoprotective potential on CCl4 induced hepatotoxicity in-vitro and in-vivo.

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Section: Resultsmentioning

confidence: 96%

Hepatoprotective potential of antioxidant potent fraction from Urtica dioica Linn. (whole plant) in CCl 4 challenged rats

2015

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“…Magnolin, an active furofuranoid lignans compound, has been reported to possess broad biological activities. Recent studies have demonstrated that magnolin shows remarkable efficacy in inhibiting tumor growth 7 , 8 , 11 , 20 . However, the exact molecular mechanisms have not been elucidated.…”

Section: Discussionmentioning

confidence: 99%

Magnolin promotes autophagy and cell cycle arrest via blocking LIF/Stat3/Mcl-1 axis in human colorectal cancers

Yin

Zhou

et al. 2018

Cell Death Dis

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Magnolin is a multi-bioactive natural compound that possesses underlying anti-cancer properties. However, the mechanisms underlying remain to be elucidated. Here, we report the role of magnolin in suppressing human colorectal cancer (CRC) cells via activating autophagy and cell cycle arrest in vitro and in vivo. Pre-treatment of cells with specific autophagy inhibitor (3-methyladenine) or knockdown of endogenous LC-3B by siRNA significantly abrogates magnolin-induced cell cycle arrest. Molecular validation mechanistically shows that magnolin-induced autophagy and cell cycle arrest in CRC cells is correlated with decreased transcriptional levels of leukemia inhibitory factor (LIF), and we further find that inhibition of LIF decreases phosphorylation level of Stat3 and represses transcriptional expression of Mcl-1. Furthermore, magnolin-induced autophagy and cell cycle arrest suppress the growth of xenograft colorectal tumors without apparent toxicity. Finally, we evaluate the clinical correlation of LIF/Stat3/Mcl-1 in CRC patient tissues. As expected, LIF, p-Stat3, and Mcl-1 levels are high in CRC tissue but are scarcely found in normal colon tissue. High positive expressions of LIF or Mcl-1 are associated with poor prognosis. Doubly positive cases have shown the worst outcome. Taken together, our results have clarified a novel molecular mechanism whereby magnolin induces autophagy and cell cycle arrest through LIF/Stat3/Mcl-1 pathway in CRCs. Our results also have revealed that magnolin has a promising therapeutic potential in CRCs.

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“…One such study was carried out against the Ehrlich ascites carcinoma in which the isolated compound Zanthonitirle showed the cytotoxic effect in dose dependent manner [30]. Another study also revealed the cytotoxic potential of lignans isolated Z. alatum against the pancreatic and lung carcinoma cell lines [31]. …”

Section: Discussionmentioning

confidence: 99%

Cytotoxic activity of extracts and crude saponins from Zanthoxylum armatum DC. against human breast (MCF-7, MDA-MB-468) and colorectal (Caco-2) cancer cell lines

Alam

Saqib

Waheed

2017

BMC Complement Altern Med

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Background Zanthoxylum armatum DC has been an important traditional plant known for its medicinal properties. It is well known for its antimicrobial, larvicidal and cytotoxic activities.MethodsThe potential anticancer effects of the methanol extract and the crude saponins from fruit, bark and leaves of Z. armatum on breast (MDA-MB-468 and MCF-7) and colorectal (Caco-2) cancer cell lines using MTT, neutral red uptake(NRU) and DAPI stain assays were evaluated.ResultsIn MTT assay the methanol extract of fruit (Zf), bark (Zb) and leaves (Zl) of Zanthoxylum armatum, showed significant and dose dependent growth inhibition of MCF-7, MDA MB-468 and Caco-2 cancer cell lines in a dose of 200 μg/ml and above. The saponins (Zf.Sa, Zb.Sa and Zl.Sa) showed significant activity against MDA MB-468 (95, 94.5 and 85.3%) as compared to MCF-7 (79.8, 9.43, 49.08%) and Caco-2 (75.8, 61.8, 68.62%) respectively. The extracts were further tested in more sensitive NRU assay and its was found that Zf extract showed higher cytotoxic activity as compared to Zb and Zl extracts with 100 μg/ml concentration. The breast cancer cell lines showed more sensitivity toward the crude saponins from fruit and bark with maximum inhibition of up to 93.81(±2.32) % with respect to 71.19(± 2.76) of Actinomycin-D. DAPI staining experiment showed that saponins from fruit induced apoptosis mode of cell death in all three types of cell lines while saponins form leaves and bark showed similar results against MDA MB-468 indicated by nuclear fragmentation and chromatin condensation. The effect of saponins from fruit, bark and leaves (Zf.Sa, Zb.Sa and Zl.Sa) against Caco-2 cell lines inhibited the growth of Caco-2 by 53.16 (±3.31) %, 66.43 (± 3.24) and 45.96 (± 10.67) respectively with respect to Actinomycin-D (4 μM) which showed the growth inhibition of 65.40(±4.29) %.ConclusionThe current study clearly demonstrates that the extract and crude saponins from fruit, bark and leaves of traditional medicinal plant Zanthoxyllum armatum DC., has the potential to exert its cytotoxic effect on cancer cell lines isolated form human by a mechanism involving apoptosis. The overall finding demonstrate that this plant specially fruits, could be potential source of new anticancer compounds for possible drug development against cancer.

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Bioactive Lignans from Zanthoxylum alatum Roxb. stem bark with cytotoxic potential

Cited by 30 publications

References 24 publications

Hepatoprotective potential of antioxidant potent fraction from Urtica dioica Linn. (whole plant) in CCl 4 challenged rats

Hepatoprotective potential of antioxidant potent fraction from Urtica dioica Linn. (whole plant) in CCl 4 challenged rats

Magnolin promotes autophagy and cell cycle arrest via blocking LIF/Stat3/Mcl-1 axis in human colorectal cancers

Cytotoxic activity of extracts and crude saponins from Zanthoxylum armatum DC. against human breast (MCF-7, MDA-MB-468) and colorectal (Caco-2) cancer cell lines

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