Discovery of New Triterpenoids Extracted from Camellia oleifera Seed Cake and the Molecular Mechanism Underlying Their Antitumor Activity

Abstract

Theasaponin derivatives, which are reported to exert antitumor activity, have been widely reported to exist in edible plants, including in the seed cake of Camellia oleifera (C.), which is extensively grown in south of China. The purpose of this study was to isolate new theasaponin derivatives from C. seed cake and explore their potential antitumor activity and their underlying molecular mechanism. In the present study, we first isolated and identified four theasaponin derivatives (compounds 1, 2, 3, and 4) from the total aglycone extract of the seed cake of Camellia oleifera by utilizing a combination of pre-acid-hydrolysis treatment and activity-guided isolation. Among them, compound 1 (C1) and compound 4 (C4) are newly discovered theasaponins that have not been reported before. The structures of these two new compounds were characterized based on comprehensive 1D and 2D NMR spectroscopy and high-resolution mass spectrometry, as well as data reported in the literature. Secondly, the cytotoxicity and antitumor property of the above four purified compounds were evaluated in selected typical tumor cell lines, Huh-7, HepG2, Hela, A549, and SGC7901, and the results showed that the ED50 value of C4 ranges from 1.5 to 11.3 µM, which is comparable to that of cisplatinum (CDDP) in these five cell lines, indicating that C4 has the most powerful antitumor activity among them. Finally, a preliminary mechanistic investigation was performed to uncover the molecular mechanism underlying the antitumor property of C4, and the results suggested that C4 may trigger apoptosis through the Bcl-2/Caspase-3 and JAK2/STAT3 pathways, and stimulate cell proliferation via the NF-κB/iNOS/COX-2 pathway. Moreover, it was surprising to find that C4 can inhibit the Nrf2/HO-1 pathway, which indicates that C4 has the potency to overcome the resistance to cancer drugs. Therefore, C1 and C4 are two newly identified theasaponin derivatives with antitumor activity from the seed cake of Camellia oleifera, and C4 is a promising antitumor candidate not only for its powerful antitumor activity, but also for its ability to function as an Nrf2 inhibitor to enhance the anticancer drug sensitivity.

TEMPO-Oxidized Nanocellulose Films Modified by Tea Saponin Derived from Camellia oleifera: Physicochemical, Mechanical, and Antibacterial Properties

“…Cellulose was obtained in the laboratory from fresh Camellia oleifera shells; tea saponins were extracted by the laboratory of Central South University of Forestry and Technology from Camellia seed cake [36], and the total aglycone extracts were used in this work. Sodium bicarbonate, sodium hypochlorite, and lithium chloride were purchased from Anhui Zesheng Technology Co., Ltd., Anhui, China; DMAc(N,N-dimethylacetamide) and DMAP(4-dimethylaminopyridine) were purchased from Shanghai Titan Technology Co., Ltd., Shanghai, China; sodium hydroxide, 2,2,6,6-tetramethylpiperidine 1-oxygen radical (TEMPO), sodium bromide, zinc acetate, and absolute ethanol were purchased from Shanghai Aladdin Biochemical Technology Co., Ltd., Shanghai, China; Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus) were purchased from Shanghai Luwei Technology Co., Ltd., Shanghai, China; and silver nitrate was purchased form Sinopharm Chemical Reagent Co., Ltd., Shanghai, China.…”

Advances in Separation, Biological Properties, and Structure–Activity Relationship of Triterpenoids Derived from Camellia oleifera Abel

“…oleifera. Figure visually shows the molecular structures of these saponins, while Table provides a concise summary of their structural properties . Specifically, these complex structures are classified as oleanane pentacyclic triterpenoids.…”

“…Notably, CoS exhibit a diverse array of beneficial properties, including anticancer, anti-inflammatory, antioxidant, antibacterial, and blood-glucose-lowering effects (Figure ). ,, This review encompasses advances in the isolation, identification, and biological activities of CoS, thus serving as a theoretical guide for the efficient utilization of processing residual products.…”

A critical review of the bioactive ingredients and biological functions of camellia oleifera oil

“…It was determined that compounds 1 and 4, namely C1 and C4, were novel saponin derivatives with anti-tumor properties. Tea saponins could be potentially viable candidates for the treatment of human ovarian cancer and breast cancer( Jia et al, 2017 ; Chen et al, 2013 ; Wu et al, 2022 ).…”