Cytotoxic and apoptotic effects of kaempferol 3-O-rhamnoside from Schima wallichii in HepG2 cells

Sep 22, 2026

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Schima wallichii is a medicinal plant with promising pharmacological potential but limited characterization. This study assessed crude extract and solvent fractions for cytotoxic effects on multiple human cancer cell lines, focusing on hepatocellular carcinoma HepG2 cells. The active fraction yielded kaempferol-3-O-rhamnoside, which suppressed cell growth and triggered apoptosis through caspase-3 activation, cell-cycle modulation, and increased cleaved caspase-3 expression. In silico docking, molecular dynamics, and DFT supported favorable binding to caspase-3, caspase-8, caspase-9, and PARP-1.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages14

Reading Time35 min

AccessFree to download

Key Findings

Cytotoxicity and apoptosis in HepG2 cells

Isolation and identification of kaempferol-3-O-rhamnoside

Mechanistic assays (caspase and cell-cycle effects)

In silico binding, stability, and electronic properties

Taxonomic and phytochemical background

Taxonomy of Schima and Apterosperma

Species distribution and biological traits

Reported phytochemicals and prior pharmacology

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN Cytotoxic and apoptotic effects ofkaempferol 3-O-rhamnoside from Schima wallichii in HepG2 cells Thuy Mi Pham Lam1, Manh DucTran1, Tan Khanh Nguyen2, Tuan Anh Le3, Van NgoThai Bich4, Tan Trung Truong5, PhuTran Vinh Pham6, Hieu PhuChi Truong7 & Manh Hung Tran7􀀍 Schima wallichii (DC.) Korth is a medicinal plant with notable pharmacological potential but remains poorly characterized. In this study, the crude extract and solvent fractions from Schima wallichii leaves were evaluated for cytotoxic activity against various human cancer cell lines. Both the total extract and its fractions exhibited dose-dependent inhibitory effects on the proliferation of hepatocellular carcinoma HepG2 cells. From the most active fraction, a major flavonoid was isolated and identified as kaempferol-3-O-rhamnoside. In vitro assays revealed that kaempferol-3-O-rhamnoside effectively suppressed HepG2 cell growth and induced apoptosis by activating caspase-3, modulating cell cycle progression, and enhancing the expression of cleaved caspase-3 protein. Complementary in silico analyses showed that K3OR bound favorably to apoptosis-related targets, including caspase-3, caspase-8, caspase-9, and PARP-1, with strong hydrogen-bonding and π-π interactions at their catalytic sites. Molecular dynamics simulations confirmed the high structural stability of the kaempferol-3-O-rhamnoside-caspase 3 complex throughout a 100-ns trajectory, while density functional theory calculations indicated a moderate HOMO-LUMO energy gap (6.48 eV), semi-soft electronic nature, and a global electrophilicity index (ω = 3.18 eV), consistent with its favorable binding reactivity. These findings suggest that K3OR exerts cytotoxic effects through caspase-mediated apoptotic activation, providing mechanistic insight into its anti-proliferative activity in liver cancer cells. Keywords Schima wallichii (DC.) Korth, Kaempferol-3-O-rhamnoside, Hepatocellular carcinoma, Apoptosis induction, Molecular docking, Molecular dynamics simulation The genus Schima (family Theaceae) has a complex taxonomic history with several nomenclatural changes over time. It was first described by Reinwardt ex Blume in 1823 but was considered invalid, and the name was later validly published in 1825–1826 for Schima noronhae Reinw. ex Blume. The status of the genus Schima was officially recognized by the Committee for Spermatophyte Nomenclature of the IAPT in 19591. Certain taxonomic issues remain unresolved, particularly since S. excelsa was once regarded as the type species but was later transferred to the genus Gordonia2,3. Morphologically, Schima species are evergreen trees bearing solitary or small clusters of terminal flowers with five petals, numerous stamens (arranged in 3–5 whorls), a five-locular ovary, and a five-lobed stigma. Schima species are widely distributed throughout Asia, with many originally described under Gordonia before being segregated into a distinct genus. In 1976, Chang et al., established the genus Apterosperma, closely related to Schima but differing in having two whorls of stamens instead of three to five and wingless seeds4. Regarding infrageneric taxonomy, Bloembergen (1952) treated Schima as a monotypic genus represented by S. wallichii with several geographically distinct subspecies5. Currently, approximately 20 Schima species are recognized, and molecular studies by Prince and Parks (2001) and Yang et al. (2004) confirmed Schima and Apterosperma as two distinct genera within Theaceae6,7. 1University of Education, The University of Danang, Danang City 550000, Vietnam. 2Scientific Management Department, Dong A University, Danang City 550000, Vietnam. 3Vietnam National Museum of Nature, VAST, 321 Huynh Thuc Khang, Hue City 49153, Vietnam. 4Faculty of Chemical Engineering, University of Science and Technology, The University of Danang, Danang City 550000, Vietnam. 5Faculty of Technology, Dong Nai

FAQs

What compound was isolated from Schima wallichii and why is it important?

A major flavonoid was isolated and identified as kaempferol-3-O-rhamnoside. It was tested for its ability to inhibit HepG2 cell growth and induce apoptosis.

How does kaempferol-3-O-rhamnoside cause apoptosis in HepG2 cells?

It induces apoptosis by activating caspase-3, modulating cell-cycle progression, and enhancing the expression of cleaved caspase-3 protein.

What computational evidence supports the anti-apoptotic target interactions?

Molecular docking suggested favorable binding to apoptosis-related targets including caspase-3, caspase-8, caspase-9, and PARP-1, and molecular dynamics confirmed structural stability of the complex. DFT calculations further indicated a moderate HOMO-LUMO gap and favorable electrophilicity for binding reactivity.

Sep 22, 2026

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