Supercritical CO2 fluid extraction of croton crassifolius Geisel root: Chemical composition and anti-proliferative, autophagic, apoptosis-inducing, and related molecular effects on A549 tumour cells
Graphical abstract
Introduction
Essential oils are natural compounds obtained from plants, the components of which are gaining increasing interest because of their relatively safe status, wide acceptance by consumers, and frequent presence in studies investigating their potential functional utility (Babahmad et al., 2018, Brasesco et al., 2017, Rakmai et al., 2018). Essential oils often act as significant indicators in evaluating the efficacy of traditional medicine (Zhang and Wang, 2009). About 300 essential oils produced from plant species are important in agricultural, food, cosmetic, and health industries (Raut and Karuppayil, 2014). As the second-leading global cause of death after cardiovascular diseases, cancer is a major public health problem (Sa et al., 2016). According to the American Cancer Society, there was an estimated 1685 210 new cancer cases diagnosed in the United States and approximately 600,000 deaths caused by the disease in 2016 (Turkez et al., 2018). There is an urgent need to discover new oncotherapy drugs that are highly effective while presenting low toxicity. It has been reported that many essential oils obtained from plants exhibit promising effects in the treatment of cancer (Song and Sun, 2016). Hence, the exploration of the anti-tumour properties of essential oils as a legitimate research focus should receive the same interest as synthetic anticancer agents (Zhang et al., 2018).
The genus Croton, which belongs to the Euphorbiaceae family, consists of approximately 1300 species that are widely distributed in tropical and sub-tropical regions (Salatino et al., 2007). Plants of this genus are rich sources of structurally diverse diterpenoids, including clerodane, trachlobane, kaurane, crotofolane, and pimarane, all of which possess broad biological activities such as cytotoxic (Giang et al., 2005), antiviral (Wang et al., 2012), antiplasmodial (Langat et al., 2011), anti-inflammatory properties (Premprasert et al., 2013), and specifics of health benefits. In addition, triterpenoids (Pan et al., 2014), flavonoids (Morales-Flores et al., 2015, Zou et al., 2012), and alkaloids (Ravanelli et al., 2016) are also occasionally found in the Croton genus.
Croton crassifolius Geisel, belonging to the Croton genus, is an economically important herb cultivated abundantly in Guangdong, Fujian and Hainan Provinces of China for commercial production of its roots in traditional Chinese medicine (Qiu, 1996). Since ancient times, its roots-known as “Ji Gu Xiang” in China-have been used in prescriptions to treat stomach ache, rheumatism, sore throat, and cancer (Committee, 1999). All the uses and treatments of different diseases are justified by the chemical composition of the plant. Previous studies investigating the chemical constituents of C. Crassifolius roots identified diverse types of diterpenes, which can be classified into clerodane, daphnane, and tigliane according to their skeletal types. Many compounds isolated from C. Crassifolius roots exhibited remarkable anticancer activity and inhibited vessel formation in zebrafish (Wang et al., 2015a, Yuan et al., 2017).
Most of studies on C. crassifolius concerned the use of root extracts in medicine, the utilization of its volatile compounds was few investigated. Huang et al. compared the anti-angiogenic activities of the two extracts (Supercritical fluid extract and steam distillation extract) from C. crassifolius. The supercritical fluid extract showed stronger effect between the two and was subject to further isolation of the active compounds in the herb. However, other anti-tumour effects including anti-proliferative, autophagy and apoptosis-inducing of the supercritical fluid extract were not mentioned (Huang et al., 2015). The objective of this study was to explore the chemical composition of CCEO extracted using supercritical CO2 fluid extraction technology, as well as the compound's potential anti-tumour activities and related anti-proliferative and apoptosis-inducing molecular mechanisms.
Section snippets
Plant materials
C. crassifolius roots were purchased in the Chinese Herbal Medicine Market in Bozhou, Anhui, China in October, 2017. The species was identified by Prof. Chenggang Shan, Institute of Agro-Food Science and Technology, Shandong Academy of Agriculture Sciences (IAFST, SAAS), Jinan, China. A voucher specimen (No.17-10-29) (Fig. 1(a)) was deposited at the Laboratory of Bioactive Substances and Functional Foods, IAFST, SAAS.
Essential oil extraction by supercritical fluid extraction
The dried and powdered roots of C. crassifolius (1.0 kg) were extracted with CO
Identification of the chemical composition of CCEO
The CCEO obtained by SFE-CO2 was yellow brown (Fig. 1(b)) frankincense oil with a yield of 3.41 ± 0.03% (w/w) based on the dry weight of C. crassifolius roots. The CCEO was analysed by GC–MS to determine volatile composition. Chemical analyses of the volatile constituents of the essential oil are summarised in Table 1 and a typical GC–MS chromatogram is shown in Fig. S1 (supplementary data). Forty compounds representing 92.90% of the total oil were identified. The main compounds were
Discussion
Abundantly cultivated in South China, C. crassifolius is a commercially-important herb in China due to its content of highly-valued bioactive compounds (e.g., diterpene in its roots). As a traditional Chinese medicine, its roots are often used to prepare many clinical treatments including anticancer drugs. In recent years, the price of C. crassifolius roots has decreased due to higher production resulting from low value-added processing. The development of novel uses for C. crassifolius is
Acknowledgments
This study was supported by the Provincial Key Research and Development Program of Shandong, China (No. 2018GNC110008); the Taishan Scholars's Program of Shandong, China; the Provincial Natural Science Foundation of Shandong of China (No. ZR2016CB51); the Agriculture Scientific and Technological Innovation Program of Shandong Academy of Agriculture Sciences (No. CXGC2018E09).
The authors would like to thank Prof. Chenggang Shan for identifying the species of C. crassifoliu.
Conflict of interest
The authors declare that they have no conflicts of interest.
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