other polar conifer bark extracts ( 80 % methanolic, aqueous ) scavenged the dpph radical with ec50 values ranging from 6. 46 ± 0. 36 to 100. 1 ± 0. 1 μg / ml [ 29, 33, 34, 35, 36 ]. in the reducing power assay, polar conifer bark extracts exhibited ec50 values ranging from 9. 17 ± 0. 13 to 25. 32 ± 0. 62 μg / ml [ 29, 35, 37 ]. overall, the ec50 values of the raw extract of cembran pine bark in the dpph and reducing power assays fall within the range of values reported for other polar conifer bark extracts. the cytotoxic potential of the raw bark extract was further investigated. hela cells were used for this purpose as they have advantages over other tumor cell lines, for example, high adaptive capacity and proliferation rate [ 38 ]. the study revealed moderate or weak cytotoxicity. at 25 and 50 μg / ml, the extract had an insignificant impact on the viability of hela cells, lacked apoptosis - inducing effects, and induced slight increases ( ≤5 % ) in the hela cell percentages in the s, g2 / m, and sub - g1 phases in comparison with the control. other polar conifer bark extracts exhibited higher activity on hela cells. the aqueous extract of pinus massoniana lamb. bark significantly inhibited hela cell viability and caused a substantial increase in the proportions of hela cells in the sub - g1 and g2 / m phases [ 39 ]. accumulation of hela cells in the sub - g1 phase is considered an indicator of a pro - apoptotic effect [ 39, 40 ]. in other studies, the extract significantly inhibited the migration and invasion of hela cells, respectively, the latter effect being attributed to cathepsin b down - regulation [ 41, 42 ]. pro - apoptotic effects in hela cells were also reported for the 80 % methanolic extract of pinus sylvestris l. bark [ 43 ], ethanolic extract of pinus merkusii jung. & de vriese bark [ 44 ], and procyanidin - rich extract of pinus koraiensis siebold & zucc. bark [ 45 ]. the pro - apoptotic effects of conifer bark extracts were found to be mediated by activation of caspase - 9 and - 3, up - regulation of the pro - apoptotic protein bax, and down - regulation of the anti - apoptotic protein bcl - 2 and survivin [ 39, 44, 45 ]. purification of the cembran pine raw bark extract resulted in the isolation of two stilbene glyco sides, namely resveratroloside ( 1 ) and pinostilbenoside ( 2 ), the structures of which were confirmed through spectroscopic techniques. to the best of our knowledge, this is the first report on the presence of resveratroloside ( 1 ) and pinostilbenoside ( 2 ) in pinus cembra l. bark. both compounds were previously isolated from other conifer barks: resveratroloside from pinus sibirica r. mayr bark [ 46 ] and pinostilbenoside from pinus sibirica r. mayr bark [ 46 ] and pinus koraiensis siebold & zucc. bark [ 18 ]. the evaluation of the antioxidant potential of resveratroloside ( 1 ) and pinostilbenoside ( 2 ) demonstrated weaker effects than the raw bark extract, indicating a potential synergistic interaction among the components of the extract. previous studies have reported similar synergistic interactions in pine bark extracts. pycnogenol, a standar diz ed extract obtained from the bark of french maritime pine ( pinus maritima lam. ), exhibits stronger biological effects than its components when tested individually [ 27 ]. in contrast to our findings, dar et al. ( 2016 ) reported a strong antioxidant potential for resveratroloside in the dpph assay ( ic50 = 14. 0 μg / ml ) [ 47 ]. the explanation lies in the fact that dar et al. [ 47 ] used another experimental protocol. resveratroloside ( 1 ) exhibited higher activity than pinostilbenoside ( 2 ) in both assays. the findings align with previous studies reporting a higher antioxidant capacity ( evaluated as oxygen radical absorbance capacity, orac ) for resveratroloside ( 4. 01 ± 0. 71 trolox equivalents / μm ) than pinostilbenoside ( 1. 89 ± 0. 25 trolox equivalents / μm ). in the same assay, the a glyco nes, resveratrol and pinostilbene, were more active than the corresponding glyco sides, showing orac values of 5. 26 ± 0. 26 and 5. 01 ± 0. 27 trolox equivalents / μm, respectively [ 48 ]. glyco sylation and methylation negatively impact the antioxidant capacity of stilbenes by blocking the free phenolic hydroxyl groups responsible for the antioxidant activity [ 49 ]. on the other hand, glyco sylation and methylation of the stilbene hydroxyl groups might enhance other bioactivities such as tyrosinase inhibitory activity [ 48 ] and anticancer activity, respectively [ 3 ]. glyco sylation enhances the stability of stilbenes, while methylation increases their lipophilicity, leading to improved bioavailability [ 3 ]. in this study, resveratroloside ( 1 ) and pinostilbenoside ( 2 ) demonstrated promising cytotoxic activity against hela cells. the activity was evaluated after 48 h of incubation with 25 or 50 μg / ml of each compound ( equivalent to 64 or 128 μm of resveratroloside ( 1 ) and 62 or 124 μm of pinostilbenoside ( 2 ) ). the selection of the concentrations to be tested and incubation time was based on previous studies investigating the cytotoxicity of resveratrol in hela cells [ 50, 51, 52 ]. in addition, this study revealed pronounced cytotoxicity ( less than 30 % cell viability ) for both compounds at 100 μg / ml. this served as additional support for selecting lower doses ( 25 and 50 μg / ml ) in cell - based assays. to the best of current knowledge, this is the first study evaluating the effects of resveratroloside ( 1 ) and pinostilbenoside ( 2 ) on human cervical carcinoma hela cells. resveratroloside ( 1 ) has been scarcely investigated for its antitumor potential. only its antiproliferative effects on h2452 malignant pleural mesothelioma cells ( approximately 30 % inhibition at 200 μm ) were reported so far [ 53 ]. to the best of our knowledge, the antitumor potential of pinostilbenoside ( 2 ) has not been investigated before. cytotoxic therapies eliminate cancer cells by triggering various pathways of cell death. induction of apoptosis ( programmed cell death ) has been a primary objective in cancer therapy for more than 30 years [ 54 ]. in recent years, many drugs, including natural compounds, have been reported to trigger other types of death in cancer cells such as autophagy, ferroptosis, necroptosis, pyroptosis, paraptosis, lyso some - dependent cell death, oncosis, and necrosis [ 55, 56 ]. resveratroloside ( 1 ) and pinostilbenoside ( 2 ) are not the sole stilbenes that cause tumor cell death by triggering non - apoptotic mechanisms. resveratrol was reported to induce tumor cell death by apoptosis, autophagy, necroptosis, and necrosis [ 56, 57 ]. pterostilbene was found to activate apoptosis, autophagy, and necrosis in cancer cells, apoptosis being the major mechanism involved in cancer cell death [ 58 ]. combrestatins ( diaryl stilbenoids ) are effective promoters of tumor necrosis [ 59 ]. dysregulation of the cell cycle, a process involving cell growth, dna replication, and cell division, is a hallmark of cancer. an important strategy in cancer therapy is the induction of cell cycle arrest. flavopiridol, abemaciclib, and palbociclib are a few examples of antitumor drugs that suppress the cell cycle via inhibition of enzymes / proteins ( cyclin - dependent kinases / cyclins ) responsible for driving the progression of the cell cycle from one phase to the next one [ 60 ]. according to this study, resveratroloside ( 1 ) and pinostilbenoside ( 2 ) impeded hela cell proliferation, with pinostilbenoside ( 2 ) being more active than resveratroloside ( 1 ) at 25 μg / ml. this result aligns with previous studies showing that stilbenes inhibit the proliferation of tumor cell lines.