Multivariate Data Analysis Guided Identification of Anticancer Constituents of Spina Gleditsiae for Human Hepatoma Cells

Abstract

Spina Gleditsia has been traditionally used as a lead ingredient of many formulas for cancer treatment in Traditional Chinese Medicine. This work aimed to reveal the phytochemical foundation of Spina Gleditsiae and underpin a fundamental understanding of its anticancer activities. The growth inhibition activities were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay of 7 solvent extracts of Spina Gleditsia in the human liver cancer cell line HepG2. The activities were then mapped onto the secondary metabolite profile of crude extracts by principal components analysis (PCA) of High Performance Liquid Chromatography-Ultraviolet (HPLC-UV) data. The top 5 PCA components of the map discriminated extract activities, mainly based on the differential content of 3 compounds. The identified compounds were then tested individually using cytotoxic assay on cancer cells in vitro. Principal components analysis constructed secondary metabolite mapping quickly identified functional compounds from the crude herbal extracts. (2 R,3 R)-7,3′,4′-Trihydroxy-5-methoxy-flavanonol, (2 R,3 R)-5,7,3′-trihydroxy-4′-methoxy-flavanonol, and isovitexin inhibited the growth of human liver cancer cell line growth with activities of 38.6 ± 1.9, 40.7 ± 0.9, and 41.5 ± 3.1 μg/mL, respectively, comparable with that of cisplatin (IC50: 41.6 ± 2.9 μg/mL). (2 R,3 R)-7,3′,4′-Trihydroxy-5-methoxy-flavanonol, (2 R,3 R)-5,7,3′-trihydroxy-4′-methoxy-flavanonol, and isovitexin are, for the first time, identified as the anticancer constituents of Spina Gleditsia. It thus strongly underpins a fundamental understanding of the anticancer activities of Spina Gleditsia and supports its ongoing clinical uses in China.

Profiling of widely targeted metabolomics for the identification of chemical composition in epidermis, xylem and pith of Gleditsiae Spina

“…Only a few bioactive substances have been reported from Gleditsiae Spina in the literature (Gao et al, 2015; Hu et al, 2020; Lee et al, 2014; Li et al, 2018; Lim et al, 2005; Yu et al, 2021; Zeng et al, 2020; Zhou et al, 2007). Flavonoids are believed to be the main metabolites and the most effective constituents in Gleditsiae Spina (Yu et al, 2021).…”

“…Pharmacological studies have revealed that Gleditsiae Spina has antioxidant, antibacterial, anti‐inflammatory and antitumor effects, and can effectively improve immunity (Cai et al, 2019; Lee et al, 2011, 2012; Li et al, 2018; Yi et al, 2015; Yoo et al, 2010; Yu et al, 2021). Flavonoids compounds are the major bioactive substances detect from Gleditsiae Spina, and they exhibit a wide range of biological activities, such as anticoagulant, antimicrobial, antiviral, antitumor, anti‐inflammatory and antidepressant effects (Hu et al, 2020; Li et al, 2010; Liu et al, 2021; Yu et al, 2021). Phenolic compounds from Gleditsiae Spina exhibit antibacterial activities (Zhou et al, 2007).…”

“…Although modern medicine and traditional medicine have proved that Gleditsiae Spina has high medicinal value, little is known about the effective ingredients. A few bioactive substances have been detected from Gleditsiae Spina, including flavonoids, phenolic acids, triterpenoids and steroids (Gao et al, 2015; Hu et al, 2020; Lee et al, 2014; Li et al, 2018; Lim et al, 2005; Yu et al, 2021; Zeng et al, 2020; Zhou et al, 2007). Most studies have focused on the identification of flavonoids.…”

“…Most studies have focused on the identification of flavonoids. Nevertheless, only about 20 flavonoids components have been detected from Gleditsiae Spina (Gao et al, 2015; Hu et al, 2020; Li et al, 2018; Yu et al, 2021; Zeng et al, 2020; Zhou et al, 2007). Moreover, no studies have focused on identifying the chemical composition in the different tissues of Gleditsiae Spina.…”

“…bioactive substances detect from Gleditsiae Spina, and they exhibit a wide range of biological activities, such as anticoagulant, antimicrobial, antiviral, antitumor, anti-inflammatory and antidepressant effects (Hu et al, 2020;Li et al, 2010;Liu et al, 2021;Yu et al, 2021).…”