Development of a standardized and effect-optimized herbal extract of Wedelia chinensis for prostate cancer

Tsai, Chin-Hsien; Tzeng, Sheue-Fen; Hsieh, Shih-Chuan; Lin, Chih‐Yu; Chen, Yet-Ran; Yang, Yu-Chih; Chou, Ya-Wen; Lee, Ming-Ting; Hsiao, Pei-Wen

doi:10.1016/j.phymed.2015.01.013

Cited by 14 publications

(16 citation statements)

References 29 publications

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“…Besides, several other compounds including common saponins and phytosterol derivatives were also reported in the species, but they appear to have a more limited distribution. Recently, several studies have demonstrated the exploration of pharmacological potential, such as analgesic [10], androgen-suppressing [11], anticancer [12, 13], antibacterial, anticonvulsant, antifungal [14], antioxidant [13], anti-inflammatory [10, 15], antiosteoprotic [16], antiulcerogenic, antistress [17], hepatoprotective [18], and sedative activities [19]. However, the investigation about the chemical constituents of W. chinensis is not sufficient compared to the other plants in the genus Wedelia .…”

Section: Introductionmentioning

confidence: 99%

α-Amylase and α-Glucosidase Inhibitory Activities of Chemical Constituents from Wedelia chinensis (Osbeck.) Merr. Leaves

Thao

Binh

Luyen

et al. 2018

Journal of Analytical Methods in Chemistry

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As part of an ongoing search for new natural products from medicinal plants to treat type 2 diabetes, two new compounds, a megastigmane sesquiterpenoid sulfonic acid (1) and a new cyclohexylethanoid derivative (2), and seven related known compounds (3–9) were isolated from the leaves of Wedelia chinensis (Osbeck.) Merr. The structures of the compounds were conducted via interpretation of their spectroscopic data (1D and 2D NMR, IR, and MS), and the absolute configurations of compound 1 were determined by the modified Mosher's method. The MeOH extract of W. chinensis was found to inhibit α-amylase and α-glucosidase inhibitory activities as well as by the compounds isolated from this extract. Furthermore, compound 7 showed the strongest effect with IC50 values of 112.8 ± 15.1 μg/mL (against α-amylase) and 785.9 ± 12.7 μg/mL (against α-glucosidase). Compounds 1, 8, and 9 showed moderate α-amylase and α-glucosidase inhibitory effects. Other compounds showed weak or did not show any effect on both enzymes. The results suggested that the antidiabetic properties from the leaves of W. chinensis are not simply a result of each isolated compound but are due to other components such as the accessibility of polyphenolic groups to α-amylase and α-glucosidase activities.

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Section: Introductionmentioning

confidence: 99%

α-Amylase and α-Glucosidase Inhibitory Activities of Chemical Constituents from Wedelia chinensis (Osbeck.) Merr. Leaves

Thao

Binh

Luyen

et al. 2018

Journal of Analytical Methods in Chemistry

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“…Apigenin and luteolin are non-toxic non-mutagenic flavonoid with potentials for cancer therapy, and widely distributed in many fruits and vegetables ( Duthie and Crozier, 2000 ; Weng and Yen, 2012 ). The dose of 10 μg/mL WCE contained about 3.4–4.9 μmol/L apigenin, 7.7–13.3 μmol/L luteolin, and 2.8–4.6 μmol/L wedelolactone ( Tsai et al, 2015 ). In LNCaP cells under androgen-containing conditions, 10 μmol/L luteolin causes 22% AR protein degradation probably through repressing chaperone HSP90, whereas 10 μmol/L apigenin downregulates AR activity without inhibiting the levels of AR mRNA and protein ( Gupta et al, 2002 ; Chiu and Lin, 2008 ).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, we standardized the preparation of this herbal extract by applying one-step purification of crude herbal extract using column chromatography to enrich the content of wedelolactone, apigenin, and luteolin to ∼70% and by lot-by-lot characterization of the enriched extract by chemical analysis and biological activity using in vitro PSA-reporter assay and in vivo tumor xenograft assay. The qualified herbal preparation was named W. chinensis extract (WCE) ( Tsai et al, 2015 ). In addition, we demonstrated that the benefit of WCE arises from synergistic suppression of the proliferation of AR-expressing PCa cells with prolonged half-lives of active compounds in blood circulation ( Tsai et al, 2009 , 2015 ).…”

Section: Introductionmentioning

confidence: 99%

“…The qualified herbal preparation was named W. chinensis extract (WCE) ( Tsai et al, 2015 ). In addition, we demonstrated that the benefit of WCE arises from synergistic suppression of the proliferation of AR-expressing PCa cells with prolonged half-lives of active compounds in blood circulation ( Tsai et al, 2009 , 2015 ). Previous evidence suggested the potential anti-cancer activity of luteolin and apigenin by downregulating the AR and AKT signaling in PCa cells ( Gupta et al, 2002 ; Chiu and Lin, 2008 ; Kaur et al, 2008 ; Shukla et al, 2014 ).…”

Section: Introductionmentioning

confidence: 99%

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A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer

et al. 2017

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Crosstalk between the androgen receptor (AR) and other signaling pathways in prostate cancer (PCa) severely affects the therapeutic outcome of hormonal therapy. Although anti-androgen therapy prolongs overall survival in PCa patients, resistance rapidly develops and is often associated with increased AR expression and upregulation of the HER2/3-AKT signaling pathway. However, single agent therapy targeting AR, HER2/3 or AKT usually fails due to the reciprocal feedback loop. Previously, we reported that wedelolactone, apigenin, and luteolin are the active compounds in Wedelia chinensis herbal extract, and act synergistically to inhibit the AR activity in PCa. Here, we further demonstrated that an herbal extract of W. chinensis (WCE) effectively disrupted the AR, HER2/3, and AKT signaling networks and therefore enhanced the therapeutic efficacy of androgen ablation in PCa. Furthermore, WCE remained effective in suppressing AR and HER2/3 signaling in an in vivo adapted castration-resistant PCa (CRPC) LNCaP cell model that was insensitive to androgen withdrawal and second-line antiandrogen, enzalutamide. This study provides preclinical evidence that the use of a defined, single plant-derived extract can augment the therapeutic efficacy of castration with significantly prolonged progression-free survival. These data also establish a solid basis for using WCE as a candidate agent in clinical studies.

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“…In vivo study showed that Wedelia chinensis extract inhibited the function of androgen receptor (AR) signaling and the tumor growth of AR-positive PCa without adverse toxicity as observed by body weight and physical activities 17 . Previously, we developed a standardized preparation of Wedelia chinensis extract (WCE) which ensures optimized effect against AR activity in PCa cells and equivalent efficacy and chemical profile in each lot 18 . In addition, we demonstrated that the context of herbal preparation improves the pharmacokinetic profile of the active compounds, wedelolactone, apigenin, and luteolin, by increasing their half-lives and therefore enhancing the tumor suppression effect compared to the formula of pure active compounds 18 .…”

Section: Introductionmentioning

confidence: 99%

A standardized herbal extract mitigates tumor inflammation and augments chemotherapy effect of docetaxel in prostate cancer

Tsai

Tzeng

Hsieh

et al. 2017

Sci Rep

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Activation of the NFκB pathway is often associated with advanced cancer and has thus been regarded as a rational therapeutic target. Wedelia chinensis is rich in luteolin, apigenin, and wedelolactone that act synergistically to suppress androgen receptor activity in prostate cancer. Interestingly, our evaluation of a standardized Wedelia chinensis herbal extract (WCE) concluded its efficacy on hormone-refractory prostate cancer through systemic mechanisms. Oral administration of WCE significantly attenuated tumor growth and metastasis in orthotopic PC-3 and DU145 xenografts. Genome-wide transcriptome analysis of these tumors revealed that WCE suppressed the expression of IKKα/β phosphorylation and downstream cytokines/chemokines, e.g., IL6, CXCL1, and CXCL8. Through restraining the cytokines expression, WCE reduced tumor-elicited infiltration of myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and endothelial cells into the tumors, therefore inhibiting angiogenesis, tumor growth, and metastasis. In MDSCs, WCE also reduced STAT3 activation, downregulated S100A8 expression and prevented their expansion. Use of WCE in combination with docetaxel significantly suppressed docetaxel-induced NFκB activation, boosted the therapeutic effect and reduced the systemic toxicity caused by docetaxel monotherapy. These data suggest that a standardized preparation of Wedelia chinensis extract improved prostate cancer therapy through immunomodulation and has potential application as an adjuvant agent for castration-resistant prostate cancer.

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Development of a standardized and effect-optimized herbal extract of Wedelia chinensis for prostate cancer

Cited by 14 publications

References 29 publications

α-Amylase and α-Glucosidase Inhibitory Activities of Chemical Constituents from Wedelia chinensis (Osbeck.) Merr. Leaves

α-Amylase and α-Glucosidase Inhibitory Activities of Chemical Constituents from Wedelia chinensis (Osbeck.) Merr. Leaves

A Standardized Wedelia chinensis Extract Overcomes the Feedback Activation of HER2/3 Signaling upon Androgen-Ablation in Prostate Cancer

A standardized herbal extract mitigates tumor inflammation and augments chemotherapy effect of docetaxel in prostate cancer

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