Cancer is the leading cause of death worldwide, and the signs of ovarian cancer, which usually manifest as bloating and abdominal pain, are not obvious and often go unnoticed [1]. In fact, more than 70 % of ovarian cancers are not diagnosed until the disease has reached stage III or IV. Therefore, despite being less prevalent than breast cancer, ovarian cancer is three times more lethal [2]. As of 2018, ovarian cancer was identified as the seventh most prevalent cancer among women globally, with approximately 2.4 million new cases reported [3]. The current standard treatment approach for ovarian cancer involves surgically reducing tumor volume, followed by cytotoxic chemotherapy utilizing a combination of carboplatin and paclitaxel. However, the significant toxicity associated with platinum-based drugs and the high cost of paclitaxel necessitate the exploration of novel treatment options. Recently, there has been a growing interest in natural products with potential for cancer treatment.

Natural products, characterized by their extensive diversity in backbone and structural complexity, play a crucial role in the process of drug discovery and development. Specifically, natural products exhibiting significant activity and possessing intriguing molecular scaffolds can serve as valuable starting points for the development of drug leads or candidates by means of structural modification and drug design [4]. C19-diterpenoid alkaloids are heterocyclic derivatives that comprise tetracyclic diterpenoids with a parent nucleus of 19 carbon atoms, connected to β-aminoethanol. The C19-diterpenoid alkaloids are renowned for their intricate structure characterized by caged and polycyclic ring systems. Diterpenoid alkaloids have great potential as new drugs for the treatment of various cancers. According to the literature published in the last decade, the antitumor activity of C19-DAs (C19-diterpenoid alkaloids) is primarily associated with the presence and location of hydroxyl and ester groups, particularly the substitutions at the C-1, 3, 6, and 8 positions [5]. The isolation and synthesis of C19-DAs have garnered significant attention within the organic chemistry community owing to their intriguing structures and diverse array of biological activities [6], [7], [8]. Thus, C19-DAs have the potential to be developed as new drug candidates to inhibit the growth of tumors.

Traditional Tibetan Medicine (TTM) is an ancient heritage encompassing herbal and spiritual healing practices that originated around the 7th century. Over the course of its development, the Tibetan medical system has assimilated theories and practices from other ethnomedical traditions such as Ayurveda and traditional Arabic medicine. Tibet's distinctive geographic and climatic conditions have fostered the abundance of remarkable medicinal herbs. However, the progress of Tibetan medicine has been hindered by geographical remoteness, limited transportation, and economic constraints, which have led to its limited understanding and development in the past. Delphinium brunonianum is a well-known medicine in the Tibetan system of medicine, it is a perennial herb, the whole herb can be used as medicine, distributed in the altitude of 4500–6000 m in the Tibetan Autonomous Region of China to Nepal and Afghanistan [9]. A noteworthy study conducted by Vijay Kumar et al. from India comprehensively assessed the tumor growth inhibitory and pro-apoptotic effects of Thapring, a Tibetan herbal formulation containing Delphinium brunonianum [10]. The study also investigated the anti-tumor effects of Thapring in a mouse model. The findings of the study revealed the pro-apoptotic and anti-cancer properties of Thapring, highlighting its potential as a promising treatment option. Nevertheless, the specific bioactive compounds responsible for their medicinal properties have not been deeply investigated. Given our interest in elucidating the underlying chemical constituents of this traditional medicine, we conducted a systematic study on the entire Delphinium brunonianum. As a result, we successfully isolated and characterized ten compounds, of which three are novel C19-DAs (compounds 1–3). This study aims to contribute to a better understanding of the material foundation of this folk medicine. Among them, compounds 1–2 are aconitine type, compound 3 is lycoctonine type, and compounds 1–6, 8–9 are the first to be discovered from D. brunonianum. The structures of the new compounds were identified by HR-ESI-MS, 1D/2D NMR spectral data and ECD calculations as well as single crystal X-Ray diffraction. Furthermore, we assessed the toxicity of these compounds against Skov-3 tumor cells using the MMT assay. In-depth in vivo and in vitro experiments were conducted specifically on compound 1 to elucidate its mechanisms of action in terms of inducing apoptosis and inhibiting proliferation.