Mohamed A. Ibrahim

The challenge of managing invasive weed species continues to affect the agricultural industry, presenting ecological, economic, and agronomic hurdles that lead to over 100 billion USD in annual crop losses globally. One such concern is the management of Agrostis stolonifera L., commonly known as creeping bentgrass, particularly due to its ability to form hybrids. This scenario underscores the urgent need for innovative, effective, and environmentally sustainable herbicides, steering the focus toward natural substances as potential candidates. We report here a promising natural lactone, commonly known as menthalactone, which is derived from Mentha piperita L. Its phytotoxic activity was assessed against the monocot, bentgrass, and a dicot, lettuce (Lactuca sativa L.). Menthalactone displayed outstanding activity against bentgrass and was further evaluated for phytotoxic characteristics. The germination of A. stolonifera seeds was significantly inhibited with an IC50 value of 4.9 ± 1.2 µM. In contrast to bentgrass seeds, Lemna pausicostata L. plants were less responsive to menthalactone treatment, shown by an IC50 of 293.4 ± 70.6 µM. Both species are monocots, and the results suggest that menthalactone might have effects on seed germination but not on the metabolism of green tissues. The susceptibility of three common, obnoxious weed species, i.e., ryegrass (Lilium perenne), barnyard grass (Echinochloa crus-galli (L.) P. Beauv.), and crabgrass (Digitaria sanguinalis (L.) Scop.), to menthalactone was assessed. Menthalactone at 1000 µM completely inhibited the germination of all three species of grasses, while 330 µM inhibited germination by less than 50%. The post-emergence application of menthalactone at 1% did not produce a significant inhibitory effect against ryegrass, barnyard grass, or crabgrass.

Machaeriols and machaeridiols are unique hexahydrodibenzopyran-type aralkyl phytocannabinoids isolated from Machaerium Pers. Earlier studies of machaeriol A (1) and B (2) did not show any affinity for cannabinoid receptor 1 (CB1 or CNR1), although they are structural analogs of psychoactive hexahydrocannabinol. This study comprehensively reports on the affinities of isolated Machaerium Pers. compounds, namely machaeriol A–D (1–4) and machaeridiol A–C (5–7), against cannabinoid (CB1 and CB2) and opioid (κ, δ and µ) receptors. Among the isolated compounds, machaeriol D (4) and machaeridiol A–C (5–7) showed some selective binding affinity for the CB2 receptor, using a radioligand binding assay, with Ki values of >1.3, >1.77, >2.18 and >1.1 μM, respectively. On the other hand, none of the compounds showed any binding to the CB1 receptor. Due to recent reports on the anticancer potential of the endocannabinoid system, compounds 1–7 were tested against a battery of luciferase reporter gene vectors that assess the activity of many cancer-related signaling pathways, including Stat3, Smad2/3, AP-1, NF-κB, E2F, Myc, Ets, Notch, FoxO, Wnt, Hedgehog and pTK in HeLa and T98G glioblastoma cells. Complete dose–response curves have been determined for each compound in both of these cell lines, which revealed that machaeridiol 6 displayed activities (IC50 in µM in HeLa and T98G cells) towards Stat3 (4.7, 1.4), Smad2/3 (1.2, 3.0), AP-1 (5.9, 4.2), NF-κB (0.5, 4.0), E2F (5.7, 0.7), Myc (5.3, 2.0), ETS (inactive, 5.9), Notch (5.3, 4.6), Wnt (4.2, inactive) and Hedgehog (inactive, 5.0). Furthermore, a combination study between machaeriol C (3) and machaeridiol B (6) displayed additive effects for E2F, ETS, Wnt and Hedgehog pathways, where these compounds individually were either minimally active or inactive. None of the compounds inhibited luciferase expression driven by the minimal thymidine kinase promoter (pTK), indicating the lack of general cytotoxicity for luciferase enzyme inhibition at the 50 µM concentration in both of these cell lines. The significance of the inhibition of these signaling pathways via machaeridiol 5–7 and their cross-talk potential has been discussed.