Cytotoxicity to Five Cancer Cell Lines of the Respiratory Tract System and Anti-inflammatory Activity of Thai Traditional Remedy

Abstract

A Thai traditional remedy called Benchalokawichian (BLW) consists of 5 plant species, Ficus racemosa, Capparis micracantha, Clerodendrum petasites, Harrisonia perforata, and Tiliacora triandra. It has long been used in Thai traditional medicine to reduce fever in respiratory tract infection, but there is no report on either cytotoxicity against cancer cell lines of the respiratory tract system or anti-inflammatory effect. Thus, the objectives of this research were to investigate the cytotoxic activity of the ethanolic and water extracts of BLW, its single plant ingredients and its isolated compounds against 5 cancer cell lines of the respiratory tract, by SRB assay. Anti-inflammatory activity of all extracts and compounds was also tested by using lipopolysaccharide-induced nitric oxide (NO) in RAW 264.7 cells. The main compounds were isolated by high-performance liquid chromatography and compared with BLW and plant ingredients. A major compound of BLW and H. perforata ethanolic extracts is perforatic acid, which inhibited the growth of 2 lung cancer cell lines, A549 and H226, with IC 50 values of 6.7 and 13.2 µg/mL. The ethanolic extract of BLW and T. triandra showed cytotoxic activity against all cancer cell lines with IC 50 values in the range of 10.1 to 45.2 µg/mL. In contrast, all EtOH extracts showed moderate anti-inflammatory activity, but the water extract had no inhibitory effect on either activity. Pectolinarigenin and O-methyllaloptaeroxyrin, 2 minor compounds, exhibited NO inhibitory effect with IC 50 values of 7.1 and 7.9 µg/mL, respectively, whereas perforatic acid was inactive (>50 µg/mL). Moreover, pectolinarigenin showed high cytotoxic activity against all cancer cell lines of the respiratory system with IC 50 values in the range of 1.9 to 9.1 µg/mL. As a result, these 2 minor compounds can be used as markers for quality control of BLW for anti-inflammatory activity. Perforatic acid and pectolinarigenin are of interest for further study on their cytotoxic mechanism. Remarkably, T. triandra, one of the plant components of BLW, is possibly the source of the active cytotoxic compounds.

The Protective Effect of Polyherbal Formulation, Harak Formula, on UVA-Induced Photoaging of Human Dermal Fibroblasts and Mouse Skin via Promoting Nrf2-Regulated Antioxidant Defense

“…Our findings strongly suggested that the photoprotective actions of HRF extracts and HSP at concentrations of 30 μg/ml and 10 μg/ml, protected against UVA-induced photoaging of NHDFs. As reported by our previous studies and others, the HRF or Benchalokawichian was demonstrated to exert the antipyretic and anti-inflammatory actions in vivo (Jongchanapong et al, 2018) as well as anti-allergic, antiinflammatory antioxidant, anti-collagenase, and depigmenting actions in vitro (Pluemsamran et al, 2013;Onkoksoong et al, 2018;Juckmeta et al, 2019;Noysang et al, 2019). Furthermore, HSP, a citrus flavonoid, has previously shown the anti-inflammatory responses and antioxidant properties by inducing the Nrf2-antioxidant defense system including the GCL and NQO-1 detoxifying antioxidant signaling as well as providing the protective effects against oxidative damage and carcinogenesis (Parhiz et al, 2015;Roohbakhsh et al, 2015;Ren et al, 2016;Biesemann et al, 2018;Ferreira de Oliveira et al, 2020).…”

“…As demonstrated by the chemical profiling of HRF and all five components (the roots of five plants used in preparation of the HRF) using the liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (LC-QTOF-MS), hesperetin (HSP) (or the (2S)-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)-2,3-dihydrochromen-4-one) was also suggested as a putative bioactive constituent of the HRF (Suebnooch et al, 2018). We and others have reported the beneficial roles of the HRF and their components in protecting against skin disorders possibly due to several pharmacological actions in vitro and in vivo including antiacne (Jantarat et al, 2018), anti-allergic (Juckmeta et al, 2014), anti-inflammatory (Juckmeta et al, 2019), antioxidant and anticollagenase (Pluemsamran et al, 2013), depigmenting (Onkoksoong et al, 2018), and wound healing properties (Mehtaa et al, 2012).…”

Determination of Lupeol, a Cytotoxic Compound Against SW620 Cells in the Extracts of Ha-Rak Recipe

“…Considering the chemical constituents of the herbal principles in the recipe, the cytotoxically active compounds such as pectolinarigenin and perforatic acid were isolated and their activities against cancer cell lines were also investigated in a recent report. 19 However, the other promising cytotoxic agents have still been explored from the plants, which are the ingredients of the recipe. Lupeol, a cytotoxic compound that was determined as one of the active compounds in C. indicum 9 was selected as an analytical marker herein, in order to examine the content in the recipe and also determine whether it was responsible for the cytotoxic activity against SW620 cell line.…”

Antiproliferative and Apoptosis-Inducing Activities of Benchalokawichian Remedy Against Doxorubicin-Sensitive and -Resistant Erythromyelogenous Leukemic Cells

“…BLW comprises the roots of five medicinal plants, including Clerodendrum petasites, Harrisonia perforata, Tiliacora triandra, Capparis micracantha, and Ficus racemosa (National Drug Committee, 2009). BLW and its herbal components consist of bioactive compounds, including alkaloids, flavonoids, and polyphenols (Brimson, Onlamoon, Tencomnao, & Thitilertdecha, 2019;Juckmeta et al, 2019;Noysang & Pummarin, 2019). Biological activities of BLW and its herbal components include anti-inflammatory, antioxidant, antimutation (Singharachai, Palanuvej, Kiyohara, Yamada, & Ruangrungsi, 2011), and antiproliferative activity against lung cancer cell lines (Juckmeta et al, 2019).…”

“…BLW and its herbal components consist of bioactive compounds, including alkaloids, flavonoids, and polyphenols (Brimson, Onlamoon, Tencomnao, & Thitilertdecha, 2019;Juckmeta et al, 2019;Noysang & Pummarin, 2019). Biological activities of BLW and its herbal components include anti-inflammatory, antioxidant, antimutation (Singharachai, Palanuvej, Kiyohara, Yamada, & Ruangrungsi, 2011), and antiproliferative activity against lung cancer cell lines (Juckmeta et al, 2019). However, the antiproliferative and apoptosis-inducing activities of BLW and its herbal components against drug-sensitive and drug-resistant cancer cells are unclear.…”