Cannabis sativa L. essential oil has attracted the interest of the scientific community thanks to its numerous biological activities. Several studies have evaluated EOs as alternative therapeutic approaches to limit the use of antibiotics; the present study aimed to evaluate the in vitro inhibitory and bactericidal activity of the essential oils obtained from the leaves and inflorescences of two hemp genotypes against twenty-one multidrug-resistant, methicillin-resistant Staphylococcus pseudintermedius strains isolated from canine clinical samples. Both EOs were mainly represented by sesquiterpene hydrocarbons, with a prevalence of β-caryophyllene and α-humulene. However, different relative amounts of phytocannabinoids were also detected. Microbiological results evidenced better outcomes for the EO characterised by the highest content of phytocannabinoids, which in turn showed no differences among the tested strains. Nevertheless, both the EOs showed better inhibitory and bactericidal activities than their main constituent, β-caryophyllene, tested individually, highlighting the presence of synergistic effects among the EO compounds.

β-Caryophyllene (BCP), a selective agonist for cannabinoid receptor 2 (CB2R), has demonstrated promising protective effects in various pathological conditions. However, the neuroprotective effects of BCP on white matter damage induced by ischemic stroke have not been elucidated previously. In this study, we find that BCP not only improves sensorimotor and cognitive function via CB2R but also mitigates white matter lesions in mice following ischemic stroke. Furthermore, BCP enhances the viability of MO3.13 oligodendrocytes after oxygen-glucose deprivation and reoxygenation (OGD/R), attenuating OGD/R-induced cellular damage and pyroptosis. Notably, these protective effects of BCP are partially enhanced by the NLRP3 inhibitor MCC950 and counteracted by the NLRP3 activator nigericin. In addition, nigericin significantly exacerbates neurological outcomes and increases white matter lesions following BCP treatment in middle cerebral artery occlusion (MCAO) mice. These results suggest that BCP may ameliorate neurological deficits and white matter damage induced by cerebral ischemia through inhibiting NLRP3-mediated pyroptosis.

Applying low-cost substrate is critical for sustainable bioproduction. Co-culture of phototrophic and heterotrophic microorganisms can be a promising solution as they can use CO2 and light as feedstock. This study aimed to create a light-driven consortium using a marine cyanobacterium Synechococcus sp. PCC 7002 and an industrial yeast Yarrowia lipolytica. First, the cyanobacterium was engineered to accumulate and secrete sucrose by regulating the expression of genes involved in sucrose biosynthesis and transport, resulting in 4.0 g/L of sucrose secretion. Then, Yarrowia lipolytica was engineered to efficiently use sucrose and produce β-caryophyllene that has various industrial applications. Then, co- and sequential-culture were optimized with different induction conditions and media compositions. A maximum β-caryophyllene yield of 14.1 mg/L was obtained from the co-culture. This study successfully established an artificial light-driven consortium based on a marine cyanobacterium and Y. lipolytica, and provides a foundation for sustainable bioproduction from CO2 and light through co-culture systems.

Ferroptosis is a form of regulated cell death triggered by iron-dependent lipid peroxidation and has been associated with heart diseases. However, there are currently no approved drugs that specifically inhibit ferroptosis in clinical practice, which largely limits the translational potential of this novel target. Here, we demonstrated that β-caryophyllene (BCP; 150 μM), a natural dietary cannabinoid, protects cardiomyocytes against ferroptotic cell death induced by cysteine deprivation or glutathione peroxidase 4 (GPX4) inactivation. Moreover, BCP preserved the mitochondrial morphology and function during ferroptosis induction. Unexpectedly, BCP supported ferroptosis resistance independent of canonical antiferroptotic pathways. Our results further suggested that BCP may terminate radical chain reactions through interactions with molecular oxygen, which also explains why its oxidation derivative failed to suppress ferroptosis. Finally, oral BCP administration (50 mg/kg, daily) significantly alleviated doxorubicin (15 mg/kg, single i.p. injection)-induced cardiac ferroptosis and cardiomyopathy in mice. In conclusion, our data revealed the role of BCP as a natural antiferroptotic compound and suggest pharmacological modification based on BCP as a promising therapeutic strategy for treating ferroptosis-associated heart disorders.

Species belonging to the genus Salvia, Lamiaceae, have been deeply involved in the folk medicine of different nations since ancient times. Lilac sage, or Salvia verticillata L. (S. verticillata) is a less studied species from the genus. However, it seems to have a prominent potential for the future drug discovery strategies of novel phytopharmaceuticals. This review aims to summarise the data on the biological activity and the phytochemical profile of extracts and essential oils derived from S. verticillata. This review is based on data from 57 in vitro and in vivo studies. The chemical profile of S. verticillata includes different synergic compounds like phenolic acids, flavonoids, terpenes, and salvianolic acids. Although some small amounts of salvianolic acid B were found in S. verticillata extracts, the major compound among the salvianolic acids is salvianolic acid C, a compound associated with the potential for improving liver fibrosis, cardio- and hepatoprotection, and the inhibition of SARS-CoV-2 infection. The cannabinoid type 2 receptor agonist β-caryophyllene is one of the major compounds in S. verticillata essential oils. It is a compound with a prominent potential in regenerative medicine, neurology, immunology, and other medical fields. The in vivo and the in vitro studies, regarding S. verticillata highlighted good antioxidant potential, anti-inflammatory, antibacterial, and antifungal activity. S.verticillata was also reported as a potential source of drug candidates for the treatment of neurodegenerative diseases such as Alzheimer\'s disease, because of the inhibitory activity on the acetylcholinesterase. However, the number of studies in this direction is limited.

Mercury chloride (ME) is a chemical pollutant commonly found in the environment, which can contribute to undesirable health consequence worldwide. The current study investigated the detrimental impact of ME on the cerebellum and spinal cord tissues in 6-8-week-old female rats. We also evaluated the neuroprotective efficacy of β-caryophyllene (BC) against spinal and cerebellar changes caused by ME. Thirty-five young Wistar albino rats were randomly chosen and assigned into five groups: control (CO), olive oil (OI), ME, BC, ME + BC. All samples were analysed by means of unbiased stereological, biochemical, immunohistochemical, and histopathological methods. Our biochemical findings showed that SOD level was significantly increased in the ME group compared to the CO group (p < 0.05). We additionally detected a statistically significant decrease in the number of cerebellar Purkinje cells and granular cells, as well as spinal motor neuron in the ME group compared to the CO group (p < 0.05). In the ME + BC group, the number of Purkinje cells, granular cells, and spinal motor neurons was significantly higher compared to the ME group (p < 0.05). Decreased SOD activity in the ME + BC group was also detected than the ME group (p < 0.05). Immunohistochemical (the tumour necrosis factor-alpha (TNF-α)) and histopathological examinations also exhibited crucial information in each of the group. Taken together, ME exposure was associated with neurotoxicity in the cerebellum and spinal cord tissues. BC treatment also mitigated ME-induced neurological alteration, which may imply its potential therapeutic benefits.

Doronicum is a relatively small genus belonging to the tribe Senecioneae (Fam. Asteraceae), distributed in Asia, Europe, and North Africa. Some of its species are considered toxic due to the presence of pyrrolizidine alkaloids whereas some other ones are largely utilised in the ethnopharmacology of several countries. In the present study, the essential oil composition of a Sicilian accession of Doronicum caucasicum M. Bieb (syn. D. orientale Hoffm.), not previously investigated, is particularly rich in sesquiterpene hydrocarbons (80.3%) with germacrene D (58.9%), α-humulene (8.8%), and β-caryophyllene (6.5%) as main metabolites. A comparison with all the essential oils from Doronicum taxa studied so far has been carried out.

This study aimed to develop a relatively natural and safe botanical insecticide for controlling the storage pest Tribolium castaneum in the egg and pupal stages. It examined how Elsholtzia densa Benth. essential oil (EO) and its primary components, β-caryophyllene and limonene, affected T. castaneum eggs and pupae through contact and fumigation. Among th, the contact activities of β-caryophyllene against T. castaneum eggs and pupae are LD50 (median lethal dose, 50%) = 0.156 mg/cm2 and ED50 (median effective dose, 50%) = 16.35 mg/pupa respectively. The study also investigated the effect of β-caryophyllene and limonene on T. castaneum eggs and pupae through synergistic contact and fumigation. When the mixing ratio of β-caryophyllene and limonene was 7:1, the LD50 value of contact activity against T. castaneum eggs was reduced to 0.100 mg/cm2, displaying an obvious synergistic effect. Experiments were conducted to investigate the antitoxic effect of β-caryophyllene on T. castaneum eggs and pupae, as well as its effects on the enzymatic activity of acetylcholinesterase, succinate dehydrogenase, glutathione S-transferase and carboxylesterase in T. castaneum pupae. Finally, the molecular docking techniques were employed to confirm the aforementioned effects on enzyme function. The findings of this study might help improve storage pest control with T. castaneum and create eco-friendly insecticides using E. densa EO, β-caryophyllene, and limonene.

BACKGROUND: Flap transplantation is a widely used plastic repair technique in surgical procedures, aimed at addressing skin defects resulting from diverse wounds and diseases. However, due to the insufficient blood supply after flap surgery, the occurrence of ischemia-reperfusion injury, and an excessive sterile inflammatory response, flaps frequently develop complications (e.g., partial or complete ischemic necrosis). These complications have adverse effects on wound healing and repair. β-Caryophyllene (BCP) is a bicyclic sesquiterpene that is widely present in plants. It mitigates oxidative stress and inflammatory responses, demonstrates neuroprotective and analgesic properties, and serves a protective function in organs or tissues subjected to ischemia-reperfusion injury. However, no study has confirmed whether BCP can be used in the field of flap transplantation to improve the flap survival rate.
METHODS: To assess the impact of BCP on random flap survival, we constructed a modified McFarlane random flap model on the rat. After 7 consecutive days of gavage with different doses of BCP, we measured the survival area ratio, angiogenesis, blood perfusion, tissue inflammation level, apoptosis-related protein levels, and the PI3K/AKT signaling pathway expression of the random flap.
RESULTS: BCP treatment increased the survival area of the flap in a dose-dependent manner after random flap transplantation in rats. BCP mainly promoted the formation of tissue blood vessels, improved flap blood perfusion, limited the local inflammatory response, and reduced apoptosis. In addition, we demonstrated that BCP works primarily by promoting the PI3K/AKT signaling expression while enhancing the phosphorylation of AKT. Administration of wortmannin, a selective inhibitor of PI3K, eliminated the effects of BCP.
CONCLUSIONS: BCP can promote the survival of random flaps by upregulating the PI3K/AKT signaling pathway, increasing tissue blood perfusion, and limiting the inflammatory response and apoptosis.

The peach fruit fly, Bactrocera zonata (Saunders) (Diptera: Tephritidae), is an economically important polyphagous quarantine pest of horticultural crops endemic to South and Southeast Asia. Methyl eugenol (ME), a naturally occurring phenylpropanoid, is a male attractant used to lure and (when mixed with an insecticide) annihilate the males from the wild population, a method of pest control termed the male annihilation technique (MAT). ME is reported to enhance the mating success of sterile males of Bactrocera spp., which is critical for enhancing the effectiveness of the sterile insect technique (SIT). The suppressed response of ME-treated males to ME-baited traps/devices allows the simultaneous application of the MAT and SIT, increasing the efficiency of area-wide integrated pest management (AW-IPM) programs. However, ME treatment in sterile males in SIT facilities is logistically difficult. β-caryophyllene (BCP) is a widely occurring, safer plant compound and is considered suitable for treating males in SIT facilities. Here, we demonstrate that BCP feeding enhanced B. zonata male mating success to the same extent as ME feeding. Feeding on BCP suppressed the male\'s subsequent attraction to ME-baited traps, but not to the same degree as feeding on ME. The results are discussed and BCP is suggested as an alternative to ME for the concurrent use of the MAT and SIT.