Cannabis sativa L. essential oil: Chemical composition, anti-oxidant, anti-microbial properties, and acute toxicity: In vitro, in vivo, and in silico study

Hawash M., Jaradat N., Salhi N.A., Shatreet B., Asbah A.A., Hawash Y.H.

AbstractThe use of traditional herbal remedies has been a common practice for centuries across different cultures to treat various ailments. In Palestine, traditional herbal medicines are widely used, but their efficacy and safety have not been thoroughly investigated. Therefore, the purpose of this study was to assess the biological activity and toxicity of two traditional herbal blends often used to treat obesity in the West Bank region of Palestine. Two herbal blends with a total of eight plants were chosen based on their historic use and availability. The plant aqueous extracts were evaluated for their antioxidant, anti-fibrotic, anti-obesity, anti-diabetic, and cytotoxic activities. The results showed that these blends have potent antifibrotic, antioxidant, and anticancer activities. While their activities on α-amylase and lipase enzymes (main targets) showed moderate activities. Therefore, our results showed that Herbal Blend 2 was more potent than Herbal Blend 1 on all investigated targets. Herbal Blend 2 showed significant activities as an antioxidant, antifibrotic, and anticancer activities with IC50 values of 68.16 ± 2.45, 33.97 ± 1.14, and 52.53 ± 0.78 µg/mL against DPPH, LX-2, and MCF-7 cell lines, respectively. While it is IC50 values on α-amylase and lipase enzymes were 243.73 ± 1.57 and 1358.39 ± 2.04 µg/mL, respectively. However, the use of anti-cancer plants can be challenging due to their cytotoxic effects on the body. We urge individuals to exercise caution when using natural remedies and to seek medical advice before incorporating them into their health regimens. This study provides valuable insight into the potential health benefits of traditional herbal remedies and emphasizes the importance of responsible usage.

Oladipo S.D., Luckay R.C., Olofinsan K.A., Obakachi V.A., Zamisa S.J., Adeleke A.A., Badeji A.A., Ogundare S.A., George B.P.

Three Schiff bases were synthesised by the condensation reaction between 2-napthaldehyde and aromatic amines to afford (E)-N-mesityl-1-(naphthalen-2-yl)methanimine (L1), (E)-N-(2,6-dimethylphenyl)-1-(naphthalen-2-yl)methanimine (L2) and (E)-N-(2,6-diisopropylphenyl)-1-(naphthalen-2-yl)methanimine (L3). The synthesised compounds were characterised using UV–visible, NMR (13C & 1H), and Fourier transform infrared spectroscopic methods while their purity was ascertained by elemental analysis. Structural analysis revealed that the naphthalene ring is almost coplanar with the imine functional group as evident by C1–C10–C11–N1 torsion angles of 176.4(2)° and 179.4(1)° in L2 and L3, respectively. Of all the various intermolecular contacts, H⋯H interactions contributed mostly towards the Hirshfeld surfaces of both L2 (58.7 %) and L3 (69.7 %). Quantum chemical descriptors of L1 - L3 were determined using Density Functional Theory (DFT) and the results obtained showed that the energy band gap (ΔE) for L1, L2 and L3 are 3.872, 4.023 and 4.004 eV respectively. The antidiabetic potential of the three compounds were studied using α-amylase and α-glucosidase assay. Compound L1 showed very promising antidiabetic activities with IC50 values of 58.85 μg/mL and 57.60 μg/mL while the reference drug (Acarbose) had 405.84 μg/mL and 35.69 μg/mL for α-amylase and α-glucosidase respectively. In-silico studies showed that L1 docking score as well as binding energies are higher than that of acarbose, which are recognized inhibitors of α-amylase together with α-glucosidase. Further insight from the RMSF, RMSD and RoG analysis predicted that, throughout the simulation L1 showcased evident influence on the structural stability of α-amylase. The antioxidant potential of the compounds was carried out using nitric oxide (NO), ferric reducing ability power (FRAP) and 2,2-diphenyl-1-picrylhydrazyl (DPPH) assays. The compounds exhibited good to fairly antioxidant properties with L1 as well as L3 having IC50 values of 70.91 and 91.21 μg/mL respectively for NO scavenging activities assay, which comparatively outshined acarbose (reference drug) with IC50 value of 109.95 μg/mL. Pharmacology and pharmacokinetics approximations of L1 – L3 showed minimal violation of Lipinski's Ro5 and this projects them to be less toxic and orally bioavailable as potential templates for the design of therapeutics with antioxidant and antidiabetic activities.

Vozza Berardo M.E., Mendieta J.R., Villamonte M.D., Colman S.L., Nercessian D.

Cannabis sativa L. (Cannabaceae) is a plant native to Eastern Asia spread throughout the world because of its medicinal properties. Despite being used for thousands of years as a palliative therapeutic agent for many pathologies, in many countries research on its effects and properties could only be carried out in recent years, after its legalization. Increasing resistance to traditional antimicrobial agents demands finding new strategies to fight against microbial infections in medical therapy and agricultural activities. Upon legalization in many countries, Cannabis sativa is gaining attention as a new source of active components, and the evidence for new applications of these compounds is constantly increasing. Extracts from five different varieties ofCannabis sativa were performed and their cannabinoids and terpenes profiles were determined by liquid and gas chromatography. Antimicrobial and antifungal activities against Gram (+) and Gram (−) bacteria, yeast and phytopathogen fungus were measured. To analyze a possible action mechanism, cell viability of bacteria and yeast was assessed by propidium iodide stain. Cannabis varieties were grouped into chemotype I and II as a consequence of their cannabidiol (CBD) or tetrahydrocannabinol (THC) content. The terpenes profile was different in quantity and quality among varieties, with (−)b-pinene, b-myrcene, p-cymene and b-caryophyllene being present in all plants. All cannabis varieties were effective to different degree against Gram (+) and Gram (−) bacteria as well as on spore germination and vegetative development of phytopathogenic fungi. These effects were not correlated to the content of major cannabinoids such as CBD or THC, but with the presence of a complex terpenes profile. The effectiveness of the extracts allowed to reduce the necessary doses of a widely used commercial antifungal to prevent the development of fungal spores. All the extracts of the analysed cannabis varieties showed antibacterial and antifungal activities. In addition, plants belonging to the same chemotype showed different antimicrobial activity, demonstrating that the classification of cannabis strains based solely on THC and CBD content is not sufficient to justify their biological activities and that other compounds present in the extracts are involved in their action against pathogens. Cannabis extracts act in synergy with chemical fungicides, allowing to reduce its doses.

Zouhri A., Bouddine T., Menyiy N.E., Kachkoul R., El-mernissi Y., Siddique F., moubachir R., Khallouki F., Salamatullah A.M., Wondmie G.F., Bourhia M., Hajji L.

AbstractThis study aims to investigate the chemical and mineral composition, antioxidant, analgesic, and anti-inflammatory effects of the aqueous extract of Cistus laurifolius var. atlanticus Pit. (Cistaceae). Additionally, molecular docking interactions of various ligands with antioxidant protein target urate oxidase (1R4U) and anti-inflammatory protein target cyclooxygenase-2 (3LN1), revealing potential dual activities and highlighting specific residue interactions. The chemical characterization focused at first glance on the mineral composition which showed that C. laurifolius extract is a mineral-rich source of potassium (K), magnesium (Mg), manganese (Mn), sodium (Na), phosphorus (P), and zinc (Zn). We next performed, ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) analysis, the latter showed various polyphenols in C. laurifolius extract including Gallic acid as the predominant polyphenol. Isoquercetin, Taxifolin and Astragalin were also among the major flavonoids detected. The antioxidant capacity of C. laurifolius leaves was tested using 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1- picrylhydrazyl (DPPH) and reducing power (RP) assays. In vitro analysis of the anti-inflammatory property of C. laurifolius leaves was conducted by the albumin denaturation test and the in vivo was assessed in the sequel by carrageenan-induced paw edema test. The analgesic activity was evaluated in vivo using tail flick, acetic acid-induced contortion, and plantar tests. The findings showed that the leave extract had a powerful antioxidant activity with an IC50 values of 2.92 ± 0.03 µg/mL (DPPH) and 2.59 ± 0.09 µg/mL (in RP test). The studied extract strongly abolished the induced inflammation (82%). Albumin denaturation test recorded an IC50 value of 210 µg/mL. Importantly, the oral administration of C. laurifolius extract considerably reduced the nociceptive effect of acetic acid in rats, showing a significant analgesic effect in a dose-related manner. Altogether, our results showed that C. laurifolius can be a promising source of phytochemicals for drug development potential.

Jagadeshbabu K., Ayodhya D., Shivaraj

Here, anisidine-based ligand (HL) and its cobalt (1a), nickel (1b) and copper (1c) complexes were synthesized and characterized by various spectroscopic techniques such as NMR, mass, IR, UV–visible, magnetic moments, ESR and TGA. The synthesized [Ni(L)2] and [Cu(L)2] complexes demonstrated square planar geometry around the metal centers, while the cobalt complex [Co(L)2(H2O)2] adopted six coordinated octahedral geometries. The DNA interaction studies of the complexes revealed an intercalative mode of binding, as evidenced by UV absorption, emission, and viscosity experiments, and the binding constant (Kb) follows the order of 1c > 1a > 1b. When exposed to oxidative and photolytic methods, the complexes demonstrated better efficacy in cleaving double-stranded pBR322 DNA compared to their parent Schiff base. When tested for cytotoxicity against A549 and MCF7 cell lines, complexes showed more activity than their parent ligand. In-vitro studies of the complexes' antimicrobial and antioxidant properties shown that they are far more effective than the parent ligand. Further, the biological efficiency of the ligand (HL) and complexes were verified by computational methods, including molecular docking (against protein data bank PDB ID: 2ADO.pdb) and pharmacokinetic studies, both the ligand (HL) and complexes have demonstrated significant potency. This promising result indicated their potential as therapeutic agents for treating pathogen-induced deformities.

Strzelecka M., Wiatrak B., Jawień P., Czyżnikowska Ż., Świątek P.

In this research, a series of novel hybrid structures of dimethylpyridine-1,2,4-triazole Schiff bases were designed, synthesized, and evaluated for their in vitro cytotoxic potency on several human gastrointestinal cancer cells (EPG, Caco-2, LoVo, LoVo/Dx, HT29) and normal colonic epithelial cells (CCD 841 CoN). Schiff base 4h was the most potent compound against gastric EPG cancer cells (CC50 = 12.10 ± 3.10 μM), being 9- and 21-fold more cytotoxic than 5-FU and cisplatin, respectively. Moreover, it was not toxic to normal cells. Regarding the cytotoxicity against colorectal cancer cells, compounds 4d and 4l exhibited good activity against HT29 cells (CC50 = 52.80 ± 2.80 μM and 61.40 ± 10.70 μM, respectively), and were comparable to or more potent than cisplatin and 5-FU. Also, they were less toxic to normal cells with a higher selectivity index (SI, CCD 841 CoN/HT29 = 4.20 and 2.85, respectively) than reference drugs (SI, CCD 841 CoN/HT29 < 1). Selected Schiff bases were subjected to the P-glycoprotein inhibition assay. Schiff bases 4d, 4e, and 4l influenced P-gp efflux function, significantly increasing the accumulation of rhodamine 123 in colon cancer cell lines. Further mechanistic studies showed that compound 4l induced apoptotic cell death through a caspase-dependent mechanism and by regulating the p53-MDM2 signaling pathway in HT29 cells. Also, physicochemical predictions of compounds 4d, 4e, 4h, and 4i were examined in silico. The results revealed that the compounds possessed promising drug-likeness profiles.

Eid A.M., Hawash M., Abualhasan M., Naser S., Dwaikat M., Mansour M.

Natural remedies derived from plants have a long history of usage in the treatment of a wide variety of severe diseases. This study aims to develop a Capparis spinosa (C. spinosa) oil nanoemulgel and evaluate its antimicrobial, anticancer, and anti-inflammatory effects. C. spinosa oil was developed into a nanoemulsion using a self-nanoemulsifying method with Span 80 and Tween 80 as emulsifying agents. Carbopol hydrogel was mixed with the nanoemulsion to form nanoemulgel. After this, we tested the particle size, polydispersity index (PDI), rheology, antimicrobial, cytotoxic, and anti-inflammatory activities. The nanoemulsion formulation that has a PDI of 0.159 and a particle size of 119.87 nm is considered to be the optimum formulation. The C. spinosa oil nanoemulgel gave results similar to its nanoemulsion, where it had a PDI lower than 0.2, droplet size below 200 nm, and zeta potential less than −35. Also, it had a pseudoplastic rheological behavior. The C. spinosa oil nanoemulgel showed a significant effect on Methicillin-Resistant Staphylococcus Aureus (MRSA) and Klebsiella pneumoniae (K. pneumonia) (ATCC 13883) with zone inhibition diameters of 33 ± 1.9 mm and 30 ± 1.4 mm, respectively, as well as significant activities on the MCF-7, HepG2, and HeLa cancer cell lines with IC50 values of 194.98, 91.2, and 251.18 µg/mL, respectively, which were better than those of the original oil. Regarding its anti-inflammatory effect, C. spinosa oil had a positive impact on both COX-1 and COX-2 but was more selective for COX-1. Consequently, simple nanotechnology techniques provide a promising step forward in the development of pharmacological dosage forms.

Aarthi S., Keerthana T., Puniethaa P.

Abstract Breast cancer is a genetically-based public health issue that affects people worldwide. The advancement of the FKBP12-rapamycin complex of the mammalian target (mTOR), the protein that is dysregulated in breast cancer, is essentially concerned with a hormone receptor. The mTORC1 and mTORC2 multiprotein complexes may be cleaved by mTOR, a serine/threonine kinase. mTOR's fap receptor movement is deregulated, which plays a part in cancer, weight, and maturing. The current study aims to acquire anti-cancer compounds from Naturally occurring Plant-based Anti-cancer Compounds (NPACT) as ligands against the target proteins of human breast cancer and identify promising hits against each target protein by analyzing ADME/T (Absorption, Distribution, Metabolism, and Excretion) properties for the chosen ligands and biomolecular interactions. Analyzing the biomolecular interactions, a pharmacophore model with a structure-based was created. and validated using Maestro 11.1. The best three compounds obtained after high-throughput screening are fap-363127 (taiwanin C), 5490349 (20-hydroxyresiniferol 9,13,14-orthophenylacetate), and 493164 (taiwanin E). The pharmacophore model displayed three main features: ARRR, Hydrogen bond acceptor, donor, and aromatic rings. Molecular Dynamics (MD) is a computer simulation technique for examining the physical fluctuations of molecular complexes using GROMACS (GROningen MAchine for Chemical Simulations). The explicit solvent model simulated the protein-ligand complexes for 100 ns. The RMSD (Root Mean Square Deviation) value of the mTOR-Benzothiazol complex ranges between 0.2 nm and 3 nm. The RMSF (Root Mean Square Fluctuation) and Rg (Radiation of gyration) are done by the highest binding compounds. This study suggests that the selected chemicals should be researched and analyzed further for breast tumor treatment and care strategies.

Judžentienė A., Garjonytė R., Būdienė J.

The phytochemistry of fibre hemp (Cannabis sativa L., cv. Futura 75 and Felina 32) cultivated in Lithuania was investigated. The soil characteristics (conductivity, pH and major elements) of the cultivation field were determined. The chemical composition of hemp extracts and essential oils (EOs) from different plant parts was determined by the HPLC/DAD/TOF and GC/MS techniques. Among the major constituents, β-caryophyllene (≤46.64%) and its oxide (≤14.53%), α-pinene (≤20.25%) or α-humulene (≤11.48) were determined in EOs. Cannabidiol (CBD) was a predominant compound (≤64.56%) among the volatile constituents of the methanolic extracts of hemp leaves and inflorescences. Appreciable quantities of 2-monolinolein (11.31%), methyl eicosatetraenoate (9.70%) and γ-sitosterol (8.99%) were detected in hemp seed extracts. The octadecenyl ester of hexadecenoic acid (≤31.27%), friedelan-3-one (≤21.49%), dihydrobenzofuran (≤17.07%) and γ-sitosterol (14.03%) were major constituents of the methanolic extracts of hemp roots, collected during various growth stages. The CBD quantity was the highest in hemp flower extracts in pentane (32.73%). The amounts of cannabidiolic acid (CBDA) were up to 24.21% in hemp leaf extracts. The total content of tetrahydrocannabinol (THC) isomers was the highest in hemp flower pentane extracts (≤22.43%). The total phenolic content (TPC) varied from 187.9 to 924.7 (average means, mg/L of gallic acid equivalent (GAE)) in aqueous unshelled hemp seed and flower extracts, respectively. The TPC was determined to be up to 321.0 (mg/L GAE) in root extracts. The antioxidant activity (AA) of hemp extracts and Eos was tested by the spectrophotometric DPPH● scavenging activity method. The highest AA was recorded for hemp leaf EOs (from 15.034 to 35.036 mmol/L, TROLOX equivalent). In the case of roots, the highest AA (1.556 mmol/L, TROLOX) was found in the extracts of roots collected at the seed maturation stage. The electrochemical (cyclic and square wave voltammetry) assays correlated with the TPC. The hydrogen-peroxide-scavenging activity of extracts was independent of the TPC.

Çapan İ., Hawash M., Jaradat N., Sert Y., Servi R., Koca İ.

Abstract Background The carbazole skeleton is an important structural motif occurring naturally or synthesized chemically and has antihistaminic, antioxidant, antitumor, antimicrobial, and anti-inflammatory activities. Objectives This study aimed to design and synthesize a novel series of carbazole derivatives and evaluate their antiproliferative and antioxidant activities. Methods The synthesized compounds were characterized utilizing HRMS, 1H-, and 13CAPT-NMR, and assessed for their anticancer, antifibrotic, and antioxidant effects utilizing reference biomedical procedures. In addition, the AutoDock Vina application was used to perform in-silico docking computations. Results A series of carbazole derivatives were synthesized and characterized in the current study. Compounds 10 and 11 were found to have a stronger antiproliferative effect than compounds 2–5 against HepG2, HeLa, and MCF7 cancer cell lines with IC50 values of 7.68, 10.09, and 6.44 µM, respectively. Moreover, compound 9 showed potent antiproliferative activity against HeLa cancer cell lines with an IC50 value of 7.59 µM. However, except for compound 5, all of the synthesized compounds showed moderate antiproliferative activities against CaCo-2 with IC50 values in the range of 43.7–187.23 µM. All of these values were compared with the positive control anticancer drug 5-Fluorouracil (5-FU). In addition, compound 9 showed the most potent anti-fibrotic compound, and the cellular viability of LX-2 was found 57.96% at 1 µM concentration in comparison with the positive control 5-FU. Moreover, 4 and 9 compounds showed potent antioxidant activities with IC50 values of 1.05 ± 0.77 and 5.15 ± 1.01 µM, respectively. Conclusion Most of the synthesized carbazole derivatives showed promising antiproliferative, antioxidant, and antifibrotic biological effects, and further in-vivo investigations are needed to approve or disapprove these results.

Adassi M.B., Ngoupaye G.T., Yassi F.B., Foutsop A.F., Kom T.D., Ngo Bum E.

Different parts of Malvaviscus arboreus Dill. Ex Cav. (M. arboreus) are traditionally used in the West Region of Cameroon to treat many diseases, including epilepsy. To determine which part of M. arboreus offers the best anticonvulsant effect, and to assess the acute and sub-acute toxicity of the part of interest. the anticonvulsant effect of the aqueous lyophilisate of the decoction of flowers, leaves, stems and roots of M. arboreus at various doses was evaluated and compared on the model of acute epileptic seizures induced by pentylenetetrazole (PTZ) (70 mg/kg), injected 1 h after oral administration of the various extracts. Out of these plant parts, the leaves were then selected to prepare the hydroethanolic extract and its anticonvulsant effect against PTZ at the doses of 122.5, 245 and 490 mg/kg, as well as its acute toxicity were compared with those of the aqueous lyophilisate of the leaves. The anticonvulsant effect of the aqueous lyophilisate of M. arboreus leaves was further evaluated on models of acute epileptic seizures induced by picrotoxin (PIC) (7.5 mg/kg), strychnine (STR) (2.5 mg/kg) and pilocarpine (350 mg/kg). The 28 days sub-acute toxicity, as well as the quantitative phytochemistry and the in vitro antioxidant potential (FRAP, DPPH, ABTS+) of the aqueous lyophilisate of the leaves of M. arboreus were also evaluated. M. arboreus leaves showed the best anticonvulsant effect and the aqueous lyophilisate was the best extract. The latter significantly protected the animals against convulsions induced by PTZ (71.43%) (p < 0.01), PIC (57.14%) (p < 0.05) and STR (42%) and had no effect on pilocarpine-induced seizures. Furthermore, it showed no acute or sub-acute toxicity, and revealed a high content of flavonoids, saponins, tannins and alkaloids, and antioxidant activity in vitro. The aqueous lyophilisate of the leaves of M. arboreus offers the best anticonvulsant effect on the extraction solvent used, and it would act mainly via a potentiation of the inhibitory systems of the brain (GABA, Glycine). In addition, its richness in bioactive compounds gives it an antioxidant potential, and it is not toxic in acute and sub-acute toxicity. All this justifies at least in part its empirical uses, and makes M. arboreus a candidate for the alternative treatment of epilepsy.

Rodríguez B.C., Durán-Zuazo V.H., García-Tejero I.F., Ruiz B.G.

Hemp is a crop that has been used since ancient times for its medicinal and textile applications, which is experiencing a resurgence today. This growing interest is due to the fact that hemp is a crop with multipurpose applications: a source of cellulosic and woody fibers, produces oil-rich seeds, is a raw material for phytochemicals and is driven by consumer demand for more natural and sustainable products. Residues recovered during the harvesting and processing of hemp fibers and/or seeds can be utilized to obtain an essential oil rich in phytochemicals with multiple applications. We review the recent progress and developments in hemp essential oil as a complex mixture of bioactive compounds with antiinflammatory, antibacterial, insecticidal and therapeutic properties, and whose exploitation can add value to hemp cultivation. Essential oils are widely used globally, and their use is constantly increasing. This could boost the utilization and market value of hemp essential oil.

Mazzara E., Petrelli R., Torresi J., Ricciardi R., Benelli G., Maggi F.

In the last decade there has been an increasing demand for hemp derivatives from legal Cannabis sativa L. (THC content < 0.3%) to be used in different industrial applications, because of the spread of its cultivation and preference in sustainable agricultural systems. In the European Union about 25,000 hectares are cultivated, and more than seventy cultivars are allowed to be grown in agricultural systems. During hemp processing a huge amount of biomass, mostly given by leaves and inflorescences, can be generated, and be reused to produce niche products. Among the latter, the essential oil, a liquid, odorous product composed mainly of monoterpenes and sesquiterpenes, represents a promising future candidate in different fields such as pest management science, pharmaceuticals, cosmetics, and others. In this chapter we review scientific literature dealing with the chemical compositions of the essential oil obtained from different cultivars of industrial hemp highlighting the potential use of their constituents as pharmaceutically active drugs, insecticides, acaricides, and antimicrobials.

Hawash M., Jaradat N., Abualhasan M., Thaher M., Sawalhi R., Younes N., Shanaa A., Nuseirat M., Mousa A.

Previously developed fluorophenyl-isoxazole-carboxamides derivatives were re-synthesized and their scavenging activity against DPPH free radical and inhibitory activity against lipase and α-amylase enzymes were evaluated. The inhibition of the tested enzymes was weak while the most potent activities were observed in the DPPH assay. In particular, compounds 2a and 2c demonstrated high antioxidant potency with IC50 values of 0.45 ± 0.21 and 0.47 ± 0.33 µg/ml, respectively, when compared to Trolox, the positive control compound, which has an IC50 value of 3.10 ± 0.92 µg/ml. Based on the in vitro results, the most potent compound 2a was chosen for in vivo evaluation of antioxidant properties using 20 male mice injected intra-peritoneally and divided into four groups. The in vivo results revealed that total antioxidant capacity (TAC) obtained for mice treated with 2a was two folds greater than that of mice treated with the positive control Quercetin. Although further biological and preclinical investigations need to be performed to assess the therapeutic potential of 2a, the results of this study show promising antioxidant activities both in vitro and in vivo.

Kumeroa F., Komahan S., Sofkova-Bobcheva S., Clavijo McCormick A.

Volatile organic compounds (VOCs) play an important role in plant ecology and can be useful in pest management. This work characterises, for the first time, the VOC emissions of six industrial hemp (Cannabis sativa L.) cultivars grown in New Zealand: CFX-2, CRS-1, Ferimon 12, Katani, Futura 75, and Finola. Volatiles emitted from flowers and foliage of eight-week-old plants were collected using a dynamic headspace sampling method and analysed using gas chromatography coupled to mass spectrometry. We assessed the effect of cultivar, sex (monoecious, male, and female), and site (i.e., two sites differing in soil types, maintained under irrigation and rain-fed conditions) on VOC emissions. Thirty-five volatile compounds were tentatively identified from the headspace samples of hemp plants, but none of the cultivars emitted all 35 compounds. β-Myrcene was the most abundant compound in most cultivars. Overall, there was a significant effect of sex, and the interaction of sex and cultivar on the volatile profiles, but no effect of site. Female plants typically emitted more volatiles than their male counterparts and monoecious cultivars. The main compounds driving the difference between cultivars and sexes were (Z)- and (E)-β-ocimene. We hypothesize that differences in emission emerged as a defence strategy to protect costly female flowers from herbivores (since C. sativa is wind pollinated), but this hypothesis needs further testing. We recommend additional studies exploring how biotic and abiotic factors influence hemp VOC emissions, changes in VOCs throughout the crop cycle, the role of VOCs in plant-insect interactions and their use in pest management.

Ghosh D., Kundu A., Chaudhary N., Gupta D., Dwivedi M., Verma R.S., Kumar B., Shanker K., Kumar N.

ABSTRACTCannabis sativa L. is an important medicinal plant with high commercial value. In recent years, the research interest in cannabidiol (CBD) and terpene‐rich cannabis has been rapidly expanding due to their high therapeutic potential. The present study aims to explore the phytocannabinoids and terpenes diversity in C. sativa collected from different parts of northern India. Our findings revealed that the cannabinoids and terpenes synthesize together in capitate stalked and capitate sessile glandular trichomes, whereas bulbous glands synthesize only terpenes. The North Indian C. sativa is mainly dominated by tetrahydrocannabinol. The CBD‐rich plant diversity is nominal (1.11%) in studied north Indian C. sativa. The essential oil profiling reveals (E)‐caryophyllene (10.30%–36.80%) as the major constituent, followed by α‐humulene (0.50%–15.29%) and α‐bisabolol (0.00%–16.40%) in the North Indian population. The cannabinoids and terpenes content showed significant diversity among and within the five studied populations. The correlation analysis between cannabinoids and terpenes indicates that α‐pinene, β‐pinene and limonene positively correlated with CBD content. Similarly, α‐ and β‐selinene correlate positively with tetrahydrocannabinolic acid content. This study could help to identify the key cultivars from India and establish a consistent chemotype for future breeding programs.

Bukowska B.

Cannabis sativa L. contains numerous compounds with antioxidant and anti-inflammatory properties, including the flavonoids and the cannabinoids, particularly Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). Cannabinoids have an effect on the endocannabinoid system (ECS), a cellular communication network, and are, hence, widely studied for medical applications. Epidiolex®, a 99% pure oral CBD extract, has been approved by the FDA for the treatment of epilepsy. Nabiximols (Sativex) is an oromucosal spray containing equal volume of THC and CBD, and it is commonly used as an add-on treatment for unresponsive spasticity in multiple sclerosis (MS) patients. Several in vitro and in vivo studies have also shown that cannabinoids can be used to treat various types of cancer, such as melanoma and brain glioblastoma; the first positive clinical trials on the anticancer effect of a THC:CBD blend with temozolomide (TMZ) in the treatment of highly invasive brain cancer are very promising. The cannabinoids exert their anticancer properties in in vitro investigations by the induction of cell death, mainly by apoptosis and cytotoxic autophagy, and the inhibition of cell proliferation. In several studies, cannabinoids have been found to induce tumor regression and inhibit angiogenic mechanisms in vitro and in vivo, as well as in two low-numbered epidemiological studies. They also exhibit antiviral effects by inhibiting ACE2 transcription, blocking viral replication and fusion, and acting as anti-inflammatory agents; indeed, prior CBD consumption (a study of 93,565 persons in Chicago) has also been associated with a much lower incidence of SARS-CoV-2 infections. It is postulated that cannabis extracts can be used in the treatment of many other diseases such as systemic lupus erythematosus, type 1 diabetes, or various types of neurological disorders, e.g., Alzheimer’s disease. The aim of this review is to outline the current state of knowledge regarding currently used medicinal preparations derived from C. sativa L. in the treatment of selected cancer and viral diseases, and to present the latest research on the potential applications of its secondary metabolites.

Idrees M., Javaid S., Nadeem S., Khurshid F., Parveen A., Malik A., Ali Khan A., Akhtar S., Fatima S.

Background Acacia nilotica is a multipurpose plant known for its remedial properties but the antimicrobial and hepatoprotective activity of its pods remained unexplored. Objective This study aimed to evaluate the antimicrobial and hepatoprotective activity of n-hexane (ANPH) and methanol (ANPM) extracts of pods to scientifically validate their medicinal claims. Methods After the pharmacognostic evaluation of pods, in vitro tests were carried out to estimate phenolic and flavonoid content and antimicrobial potential. In vivo experiments involved testing of both extracts (250 and 500 mg/kg) paracetamol (PCM)-induced hepatotoxicity model in rats. The molecular docking studies explored insights into the potential binding capabilities of the ligands with the specific target proteins. Results ANPH and ANPM were enriched with phenols and flavonoids and showed antimicrobial effects. In the hepatoprotective test, the rats chronically treated with extracts had a dose-dependent hepatoprotection as markers of liver functionality were notably reduced ( P < 0.05). The in silico studies revealed strong binding interactions of ergost-5-en-3-ol and oxiranyl methyl ester 9-octadecenoic acid with target proteins for antibacterial activity and hepatoprotective activity, respectively. Conclusion The antimicrobial and hepatoprotective potential of pods might be due to their phenols and flavonoids. The Pyrogallol, Ergost-5-en-3-and 9-octadecenoic acid might be bringing these remedial benefits through antioxidant and anti-inflammatory effects.

Batool Z., Ullah S., Khan A., Siddique F., Nadeem S., Alshammari A., Albekairi N.A., Talib R., Al-Harrasi A., Shafiq Z.

Developing new anti-tyrosinase drugs seems crucial for the medical and industrial fields since irregular melanin synthesis is linked to the resurgence of several skin conditions, including melanoma, and the browning of fruits and vegetables.