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探讨 Prasachandaeng 疗法及其生物活性化合物的体外抗增殖和抗炎活性。

Exploring in vitro anti-proliferative and anti-inflammatory activities of Prasachandaeng remedy, and its bioactive compounds.

机构信息

Department of Applied Thai Traditional Medicine and Center of Excellence in Applied Thai Traditional Medicine Research (CEATMR), Faculty of Medicine, Thammasat University (Rangsit Campus), Klong Luang, Pathum Thani, 12120, Thailand.

Region Medicine Science Center 12 Songkhla, Department of Medical Science, Songkhla, 90110, Thailand.

出版信息

BMC Complement Med Ther. 2022 Aug 11;22(1):217. doi: 10.1186/s12906-022-03678-y.

Abstract

BACKGROUND

Prasachandaeng (PSD) remedy has been empirically used in Thai traditional medicine to treat fever in bile duct and liver and cancer patients through Thai folk doctors. However, there have been no scientific reports on the bioactive compounds and bioactivities related to inflammation-associated carcinogenesis or cytotoxicity against cancer cell lines. In this study, we investigated the chemical content of the remedy, and evaluated its cytotoxic activity against two cancer cell lines in comparison with a non-cancerous cell line and determined tumor necrosis factor-alpha (TNF-α) production in a murine macrophage cell line (RAW 264.7) to evaluate anti-inflammatory activity. A novel HPLC method was used for quality control of its chemical content.

METHODS

Pure compounds from the EtOH extract of D. cochinchinensis were isolated using bioassay-guided fractionation and chemical content of the PSD remedy was determined using HPLC. The cytotoxic activity against the hepatocarcinoma cell line (HepG2) and cholangiocarcinoma cell line (KKU-M156), in comparison with non-cancerous cell line (HaCaT), were investigated using antiproliferative assay (SRB). The anti-inflammatory activity measured by TNF-α production in RAW 264.7 was determined using ELISA.

RESULTS

All crude extracts and isolated compounds exhibited significant differences from vincristine sulfate (p < 0.0001) in their cytotoxic activity against HepG2, KKU-M156, and HaCaT. The PSD remedy exhibited cytotoxic activity against HepG2 and KKU-M156 with IC values of 10.45 ± 1.98 (SI = 5.3) and 4.53 ± 0.74 (SI = 12.2) µg/mL, respectively. Some constituents from C. sappan, D. cochinchinensis, M. siamensis, and M. fragrans also exhibited cytotoxic activity against HepG2 and KKU-M156, with IC values less than 10 µg/mL. The isolated compounds, i.e., Loureirin B (1), 4-Hydroxy-2,4'-dimethoxydihydrochalcone (2), and Eucomol (3) exhibited moderate cytotoxicity against two cancer cell lines. None of the crude extracts and isolated compounds showed cytotoxicity against HaCaT. D. cochinchinensis and PSD remedy exhibited higher anti-inflammatory activity measured as TNF-α production than acetaminophen.

CONCLUSION

The findings provide evidence of bioactivity for EtOH extracts of PSD remedy and the isolated compounds of D. Cochinchinensis. The results consistent the use clinical activity and use of PSD remedy as a antipyretic treatment for liver and bile duct cancer patients by Thai traditional practitioners.

摘要

背景

Prasachandaeng (PSD) 疗法在泰国传统医学中被经验性地用于治疗胆管和肝脏发热以及癌症患者,方法是通过泰国民间医生使用。然而,目前还没有关于与炎症相关的致癌作用或细胞毒性相关的生物活性化合物和生物活性的科学报告,也没有针对癌细胞系的生物活性化合物和生物活性的科学报告。在这项研究中,我们研究了该疗法的化学成分,并评估了其对两种癌细胞系的细胞毒性活性,与非癌细胞系进行了比较,并确定了在 RAW 264.7 小鼠巨噬细胞系中肿瘤坏死因子-α (TNF-α) 的产生,以评估抗炎活性。使用新型 HPLC 方法对其化学含量进行质量控制。

方法

使用生物测定指导的分步分离从 D. cochinchinensis 的 EtOH 提取物中分离出纯化合物,并使用 HPLC 测定 PSD 疗法的化学含量。使用 SRB 法测定对肝癌细胞系 (HepG2) 和胆管癌细胞系 (KKU-M156) 的细胞毒性活性,与非癌细胞系 (HaCaT) 进行比较。使用 ELISA 测定 RAW 264.7 中 TNF-α 产生的抗炎活性。

结果

所有粗提取物和分离出的化合物在对 HepG2、KKU-M156 和 HaCaT 的细胞毒性活性方面均与硫酸长春新碱 (p < 0.0001) 有显著差异。PSD 疗法对 HepG2 和 KKU-M156 具有细胞毒性活性,IC 值分别为 10.45 ± 1.98 (SI = 5.3) 和 4.53 ± 0.74 (SI = 12.2) µg/mL。来自 C. sappan、D. cochinchinensis、M. siamensis 和 M. fragrans 的一些成分也对 HepG2 和 KKU-M156 具有细胞毒性活性,IC 值小于 10 µg/mL。分离出的化合物,即 Loureirin B (1)、4-羟基-2,4'-二甲氧基二氢查耳酮 (2) 和 Eucomol (3) 对两种癌细胞系具有中等细胞毒性。没有一种粗提取物和分离出的化合物对 HaCaT 表现出细胞毒性。D. cochinchinensis 和 PSD 疗法在 TNF-α 产生方面表现出比醋氨酚更高的抗炎活性。

结论

这些发现为 PSD 疗法的 EtOH 提取物和 D. Cochinchinensis 的分离化合物的生物活性提供了证据。结果一致表明,泰国传统从业者将 PSD 疗法作为治疗胆管和肝癌患者发热的方法,具有临床活性和用途。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f4ad/9373486/016607a23b4e/12906_2022_3678_Fig1_HTML.jpg

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