Four new highly oxidized caryophyllene-type sesquiterpenes (1–4), one new caryophyllene-type natural product (5), and two new drimane-type sesquiterpenes (6, 7), along with eight known compounds have been isolated from an endophytic fungus Pestalotiopsis adusta. Their structures were elucidated on the basis of HRESIMS, 1D and 2D NMR spectroscopic data analyses. The absolute configurations for 1 and 5 were determined by single-crystal X-ray crystallographic analysis using Cu Kα radiation. The absolute configuration of 6 was determined by CD spectrum associated with TD-DFT calculation of its benzoylated derivative 6a. The in vitro bioassay revealed that 8 and 9 presented cytotoxicity against cancer cell lines A549, HeLa, and SMMC-7721, in which 8 showed comparable activity (IC₅₀ = 28.3 μM) to the positive control etoposide (IC₅₀ = 23.2 μM) against SMMC-7721.

Osmanthus fragrans has been used as folk medicine for thousands of years. The extracts of Osmanthus fragrans flowers were reported to have various bioactivities including free radical scavenging, anti-inflammation, neuroprotection and antitumor effects. However, there is still lack of knowledge about its essential oil. In this work, we analyzed the chemical composition of the essential oil from Osmanthus fragrans var. thunbergii by GC-MS. A complex network approach was applied to investigate the interrelationships between the ingredients, target proteins, and related pathways for the essential oil. Statistical characteristics of the networks were further studied to explore the main active ingredients and potential bioactivities of O. fragrans var. thunbergii essential oil. A total of 44 ingredients were selected from the chemical composition of O. fragrans var. thunbergii essential oil, and that 191 potential target proteins together with 70 pathways were collected for these compounds. An ingredient-target-pathway network was constructed based on these data and showed scale-free property as well as power-law degree distribution. Eugenol and geraniol were screened as main active ingredients with much higher degree values. Potential neuroprotective and anti-tumor effect of the essential oil were also found. A core subnetwork was extracted from the ingredient-target-pathway network, and indicated that eugenol and geraniol contributed most to the neuroprotection of this essential oil. Furthermore, a pathway-based protein association network was built and exhibited small-world property. MAPK1 and MAPK3 were considered as key proteins with highest scores of centrality indices, which might play an important role in the anti-tumor effect of the essential oil. This work predicted the main active ingredients and bioactivities of O. fragrans var. thunbergii essential oil, which would benefit the development and utilization of Osmanthus fragrans flowers. The application of complex network theory was proved to be effective in bioactivities studies of essential oil. Moreover, it provides a novel strategy for exploring the molecular mechanisms of traditional medicines.