Poly (ADP-ribose) polymerase (PARP) is a nuclear enzyme that catalyzes poly (ADP-ribose) ribosylation in eukaryotic cells. The poly (ADP-ribose) polymerase (PARPs) family is composed of at least 17 members, which participate in poly (ADP-ribose) cleavage, one of the most important post-translational modifications of proteins [1]. PARP1, which accounts for more than 80 % of PARP activity in cells, is widely distributed in organisms and plays an important role in physiological processes such as DNA damage repair, gene transcription and expression, and apoptosis [2]. BRCA1 protein is one of the main functional proteins of the homologous recombination repair (HR) pathway, which plays an important role in DNA double-strand break repair. BRCA1-deficient tumor cells are sensitive to PARP inhibitors due to their synergistic lethal effect [3]. Therefore, more and more studies have begun to focus on the role of PARP inhibitors in cancer therapy [4]. Olaparib was approved as the first PARP1 inhibitor for cancer treatment, which finally established this anti-cancer strategy in the clinic [5].

In clinical research, PARP inhibitor (Olaparib) is mainly used for the treatment of BRCA-deficient cancers, such as ovarian cancer and breast cancer. However, patients taking Olaparib often experience side effects such as nausea, fatigue, vomiting, and anemia [6]. Obtaining anticancer drugs from natural products is a hot field in the development of cancer drugs. Natural products, as an important source of molecularly targeted drugs, have the characteristics of novel and diverse structures and unique biological activities [7]. With the help of pharmaceutical chemistry and other methods, they can be structurally modified, modified, and optimized to obtain new chemical entities with resistance and minimal toxic side effects [8]. This can provide new ideas for breaking through the bottleneck of molecular-targeted drug development [9]. Ginsenoside 3β,12β,21α,22β-Hydroxy-24-norolean-12-ene (G-M6, the structure is shown in Fig. 1A), a phase I metabolite of antitumor compound 20(R)-25-methoxyldammarane-3β,12β,20-triol (AD-1), had the most significant inhibitory effect on the growth of a variety of cancer cells, especially on the ovarian cancer cell line, which was stronger than the parent drug [10]. Molecular docking studies have shown that G-M6 can effectively bind to PARP-1, which may provide a new solution for searching for PARP inhibitors [11].

Based on previous research, this study further demonstrated the simulation results of the stability of the G-M6-PARP complex using computational biology methods and demonstrated the actual binding characteristics of G-M6 and PARP protein through surface plasmon resonance (SPR). The inhibitory effects of G-M6 on PARP1 and 14 tyrosine kinases were evaluated at the molecular level. At the cellular level, the inhibitory effect of G-M6 on the proliferation of tumor cell lines with complete/deficient homologous recombination and its sensitization effect on the cytotoxic drug taxol were investigated. The in vivo anti-tumor activity of G-M6 was investigated in nude mouse transplantation models of human ovarian cancer UWB1.289 (BRCA1−/−) and BRCA-improved SW620. This study proposes for the first time that G-M6 is a potent and highly selective PARP1 inhibitor with significant in vitro and in vivo anti-tumor activity against tumors with homologous repair defects, which is of great significance for the development of targeted ovarian cancer drugs.