Combinations of Cannabinoids with Silver Salts or Silver Nanoparticles for Synergistic Antibiotic Effects against Methicillin-Resistant Staphylococcus aureus

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“Silver has been shown to improve the antibiotic effects of other drugs against both Gram- positive and -negative bacteria. In this study, we investigated the antibiotic potential of cannabidiol (CBD), cannabichromene (CBC) and cannabigerol (CBG) and their acidic counterparts (CBDA, CBCA, CBGA) against Gram-positive bacteria and further explored the additive or synergistic effects of silver nitrate or silver nanoparticles using 96-well plate growth assays and viability (CFUs- colony-forming units).

All six cannabinoids had strong antibiotic effects against MRSA with minimal inhibitory concentrations (MICs) of 2 mg/L for CBG, CBD and CBCA; 4 mg/L for CBGA; and 8 mg/L for CBC and CBDA. Using 96-well checkerboard assays, CBC, CBG and CBGA showed full or partial synergy with silver nitrate; CBC, CBDA and CBGA were fully synergistic with silver nanoparticles against MRSA.

Using CFU assays, combinations of CBC, CBGA and CBG with either silver nitrate or silver nanoparticles, all at half or quarter MICs, demonstrated strong, time-dependent inhibition of bacterial growth (silver nitrate) and bactericidal effects (silver nanoparticles). These data will lead to further investigation into possible biomedical applications of specific cannabinoids in combination with silver salts or nanoparticles against drug-resistant Gram-positive bacteria.”

https://pubmed.ncbi.nlm.nih.gov/38927140/

“In conclusion, these studies confirm the antibiotic activity of CBG, CBC and CBD and the acidic forms of these agents against drug-resistant Gram-positive bacteria. The addition of silver, either as salts or nanoparticles, to select cannabinoids allows for much improved and, in some cases, synergistic antibiotic activity. Collectively, these findings strongly support further investigation of cannabinoid-enhanced silver preparations to assess their antimicrobial spectrum of activity and potential application in wound dressings or catheter coatings for an extended and more powerful antibiotic profile.”

https://www.mdpi.com/2079-6382/13/6/473

Feature-Based Molecular Network-Assisted Cannabinoid and Flavonoid Profiling of Cannabis sativa Leaves and Their Antioxidant Properties

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“Cannabis sativa (C. sativa) leaves are rich in cannabinoids and flavonoids, which play important antioxidant roles.

Since the environmental factors may influence the accumulation of antioxidants in herbal medicines, which affects their activity, this study aimed to investigate the correlation between the chemical composition of C. sativa leaves and their geographical origin and antioxidant activity. Firstly, a high-resolution mass spectrometry method assisted by semi-quantitative feature-based molecular networking (SQFBMN) was established for the characterization and quantitative analysis of C. sativa leaves from various regions. Subsequently, antioxidant activity analysis was conducted on 73 batches of C. sativa leaves, and a partial least squares regression (PLS) model was employed to assess the correlation between the content of cannabinoids and flavonoids in the leaves and their antioxidant activity.

A total of 16 cannabinoids and 57 flavonoids were annotated from C. sativa, showing a significant regular geographical distribution. The content of flavonoid-C glycosides in Sichuan leaves is relatively high, and their antioxidant activity is also correspondingly high. However, the leaves in Shaanxi and Xinjiang were primarily composed of flavonoid-O glycosides, and exhibited slightly lower antioxidant activity.

A significant positive correlation (p < 0.001) was found between the total flavonoids and cannabinoids and the antioxidant activity of the leaves, and two flavonoids and one cannabinoid were identified as significant contributors.”

https://pubmed.ncbi.nlm.nih.gov/38929189/

“The antioxidant activity exhibited by C. sativa leaves is correlated with the content of cannabinoids and flavonoids inside.”

https://www.mdpi.com/2076-3921/13/6/749

Evidence of Cannabidiol Effectiveness Associated or Not with Tetrahydrocannabinol in Topical Administration: A Scope Review

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“Cannabis sativa is a plant of the Cannabaceae family, whose molecular composition is known for its vast pharmacological properties. Cannabinoids are the molecules responsible for Cannabis sativa potential effects, especially tetrahydrocannabinol and cannabidiol.

Scientific development has shown interest in the potential of cannabidiol in various health conditions, as it has demonstrated lower adverse events and great pharmacological potential, especially when administered topically.

The present study aims to carry out a scoping review, focusing on the use of cannabidiol, in vivo models, for topical administration. Thus, the methodological approach used by the Joanna Briggs Institute was applied, and the studies were selected based on previously established inclusion criteria.

Even though more information regarding the dose to achieve pharmacological potential is still needed, cannabidiol demonstrated potential in treating and preventing different conditions, such as glaucoma, atopic dermatitis, epidermolysis bullosa, and pyoderma gangrenosum.”

https://pubmed.ncbi.nlm.nih.gov/38931415/

https://www.mdpi.com/1424-8247/17/6/748

Cannabinol Regulates the Expression of Cell Cycle-Associated Genes in Motor Neuron-like NSC-34: A Transcriptomic Analysis

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“Cannabinoids are reported to have neuroprotective properties and play a role in neurogenesis and neuroplasticity in in vitro and in vivo models. Cannabinol (CBN) is a minor cannabinoid produced by the degradation of Δ9-tetrahydrocannabinol in Cannabis sativa L. and exhibits anti-oxidant, analgesic, anti-bacterial, and anti-inflammatory effects.

In this study, we explored the biological effects of 20 µM CBN (6.20 µg/mL) on differentiated NSC-34 cells by MTT assay and next-generation sequencing analysis on the transcriptome. KEGG and Gene Ontology enrichment analyses have been performed to evaluate potential CBN-associated processes.

Our results highlighted the absence of any cytotoxic effect of CBN. The comparative transcriptomic analysis pointed out the downregulation of Cdkn2aCdkn2c and Cdkn2d genes, which are known to suppress the cell cycle. Ccne2Cdk2Cdk7Anapc11Anapc10Cdc23Cdc16Anapc4Cdc27Stag1Smc3Smc1aNipblPds5aPds5b, and Wapl genes, renowned for their role as cell cycle progression activators, were instead upregulated. Our work suggests that CBN regulates the expression of many genes related to the cell cycle, which are required for axonal maturation, migration, and synaptic plasticity, while not affecting the expression of genes involved in cell death or tumorigenesis.”

https://pubmed.ncbi.nlm.nih.gov/38927547/

“The results obtained could be a starting point for testing CBN on models of motor neuron diseases characterized by synaptic dysfunctions and aberrant reactivation of the cell cycle leading to cell death.”

https://www.mdpi.com/2227-9059/12/6/1340

Spent Material Extractives from Hemp Hydrodistillation as an Underexplored Source of Antimicrobial Cannabinoids

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“Hemp (Cannabis sativa L.) has been used for millennia as a rich source of food and fibers, whereas hemp flowers have only recently gained an increased market interest due to the presence of cannabinoids and volatile terpenes. Currently, the hemp flower processing industry predominantly focuses on either cannabinoid or terpene extraction.

In an attempt to maximize the valorization of hemp flowers, the current study aimed to evaluate the phytochemical composition and antimicrobial properties of several extracts obtained from post-distillation by-products (e.g., spent material, residual distillation water) in comparison to the essential oil and total extract obtained from unprocessed hemp flowers.

A terpene analysis of the essential oil revealed 14 monoterpenes and 35 sesquiterpenes. The cannabinoid profiling of extracts showed seven acidic precursors and 14 neutral derivatives, with cannabidiol (CBD) reaching the highest concentration (up to 16 wt.%) in the spent material extract. The antimicrobial assessment of hemp EO, cannabinoid-containing extracts, and single compounds (i.e., CBD, cannabigerol, cannabinol, and cannabichromene) against a panel of 20 microbial strains demonstrated significant inhibitory activities against Gram-positive bacteria, Helicobacter pylori, and Trichophyton species.

In conclusion, this work suggests promising opportunities to use cannabinoid-rich materials from hemp flower processing in functional foods, cosmetics, and pharmaceuticals with antimicrobial properties.”

https://pubmed.ncbi.nlm.nih.gov/38927152/

“Considering that the hemp flower essential oil industry generates significant amounts of unused biomass rich in cannabinoids, the strategy implemented in the current work could afford high-added-value by-products within the hemp production chain, contributing to the principles of the circular economy and sustainability. Altogether, this work can open promising avenues for utilizing cannabinoid-rich materials obtained during hemp flower processing in functional foods or cosmeceutical and pharmaceutical products with antimicrobial properties.”

https://www.mdpi.com/2079-6382/13/6/485

Effects of medical cannabis use on physical and psychiatric symptoms across the day among older adults

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“Introduction: Older adults are increasingly using medical cannabis (MC). It is unclear if therapeutic effects increase problematic use patterns. The current study addresses this issue by examining symptom trajectories across the day and using trajectories to predict problematic use.

Methods: One-hundred six older adults (age range 55-74) who endorsed medical conditions approved for treatment using MC were recruited online. Participants received six text messages/day to assess momentary symptoms for 15 days.

Results: Participants provided 5,156 momentary assessments across 1,106 use days. Symptom trajectories were examined across the day. There was a decline in all symptoms following use. Negative affect, pain, and nausea evinced momentary negative reinforcement associations with cannabis intoxication. Momentary negative reinforcement was associated with adverse cannabis outcomes. Declines in post-use trauma symptoms and momentary negative reinforcement effects for negative affect were both associated with cannabis use disorder symptoms.

Discussion: These data suggest that MC may be effective in reducing common symptom clusters. However, the negative reinforcing effect (i.e., the link between use and symptom relief at the event level) may complicate the therapeutic nature (i.e., symptom reduction). Identifying interventions to maximize benefits while minimizing costs may increase the efficacy and safety of MC in older adults.”

https://pubmed.ncbi.nlm.nih.gov/38924900/

“Medical cannabis (MC) use is increasing in older adults. MC was associated with decreases in pain, negative affect, trauma, and nausea.”

https://www.sciencedirect.com/science/article/abs/pii/S0165178124003408?via%3Dihub


The Therapeutic Potential of Hemp Seed Oil in D-Galactose-Induced Aging Rat Model Was Determined through the Combined Assessment of 1H NMR Metabolomics and 16S rRNA Gene Sequencing

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“Aging is an irreversible process of natural degradation of bodily function. The increase in the aging population, as well as the rise in the incidence of aging-related diseases, poses one of the most pressing global challenges.

Hemp seed oil, extracted from the seeds of hemp (Cannabis sativa L.), possesses significant nutritional and biological properties attributed to its unique composition of polyunsaturated fatty acids and various antioxidant compounds. However, there is limited knowledge regarding the anti-aging mechanism of hemp seed oil.

This study aimed to evaluate the beneficial effects and potential mechanisms of hemp seed oil in a D-galactose (D-gal)-induced aging rat model through a combined analysis of metabolomics and 16S rRNA gene sequencing.

Using nuclear magnetic resonance (NMR)-based metabolomics, significant alterations in serum and urine metabolic phenotypes were observed between the D-gal-induced aging rat model and the healthy control group. Eight and thirteen differentially expressed metabolites related to aging were identified in serum and urine, respectively.

Treatment with hemp seed oil significantly restored four and ten potential biomarkers in serum and urine, respectively. The proposed pathways primarily included energy metabolism, amino acid metabolism, one-carbon metabolism, and lipid metabolism. Furthermore, 16S rRNA gene sequencing analysis revealed significant changes in the gut microbiota of aged rats. Compared to the model group, the hemp seed oil group exhibited significant alterations in the abundance of 21 bacterial taxa at the genus level.

The results indicated that hemp seed oil suppressed the prevalence of pathogenic bacterial genera such as StreptococcusRothia, and Parabacteroides. Additionally, it facilitated the proliferation of the genera Lachnospirace_NK4B4_group and Lachnospirace_UCG_001, while also enhancing the relative abundance of the genus Butyricoccus; a producer of short-chain fatty acids (SCFAs).

These findings provided new insights into the pathogenesis of aging and further supported the potential utility of hemp seed oil as an anti-aging therapeutic agent.”

https://pubmed.ncbi.nlm.nih.gov/38921439/

“In conclusion, this study demonstrated that the administration of hemp seed oil resulted in a reversal of 4 and 10 differential metabolites related to aging in the serum and urine of the model rats, respectively. These findings suggested that hemp seed oil exerted anti-aging effects by partially restoring the balance of disrupted metabolic pathways, including energy metabolism, amino acid metabolism, one-carbon metabolism, and lipid metabolism. These results provided novel insights into the pathogenesis of aging and further supported the potential therapeutic use of hemp seed oil as an anti-aging intervention.”

https://www.mdpi.com/2218-1989/14/6/304

In vivo and in silico studies of the effects of oil extracted from Cannabis sativa L. seeds on healing of burned skin wounds in rats

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“Introduction: This study investigates the potential effects of cannabis seed oil (CSO) on the wound healing process. The aim was to assess the efficacy of CSO in treating skin wounds using an animal model and to explore its anti-inflammatory properties through in silico analysis.

Methods: Eighteen male albino Wistar rats, weighing between 200 and 250 g, were divided into three groups: an untreated negative control group, a group treated with the reference drug silver sulfadiazine (SSD) (0.01 g/mL), and a group treated topically with CSO (0.962 g/mL). The initial wound diameter for all groups was 1 cm. In silico studies were conducted using Maestro 11.5 to evaluate the anti-inflammatory effects of phytoconstituents against cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2).

Results: CSO and SSD treatments led to a significant reduction (p <0.05) in the size of burned skin wounds by day 5, with contraction rates of 53.95% and 45.94%, respectively, compared to the untreated negative control group. By day 15, wounds treated with CSO and SSD had nearly healed, showing contraction rates of 98.8% and 98.15%, respectively. By day 20, the wounds treated with CSO had fully healed (100%), while those treated with SSD had almost completely healed, with a contraction rate of 98.97%. Histological examination revealed granulated tissue, neo-blood vessels, fibroblasts, and collagen fibers in wounds treated with CSO. In silico studies identified arachidic acid, γ-linolenic acid, and linolenic acid as potent inhibitors of COX-1 and COX-2. Serum biochemical parameters indicated no significant changes (p > 0.05) in liver and kidney function in rats treated with CSO, whereas a significant increase (p < 0.01) in ALAT level was observed in rats treated with SSD.

Discussion: The findings demonstrate that CSO has a promising effect on wound healing. The CSO treatment resulted in significant wound contraction and histological improvements, with no adverse effects on liver and kidney function.However, the study’s limitations, including the small sample size and the need for detailed elucidation of CSO’s mechanism of action, suggest that further research is necessary. Future studies should focus on exploring the molecular pathways and signaling processes involved in CSO’s pharmacological effects.”

https://pubmed.ncbi.nlm.nih.gov/38919274/

“The results of the present study demonstrated the efficacy of CSO in the healing of burn wounds in rats, indicating it might represent a natural compound that can be used to treat injuries to the skin in humans and animals. CSO can also be an excellent drug in the cosmetic field because of its potential protection against skin problems via its efficacy in cicatrization. The results presented here provide the basis for future clinical studies demonstrating the safety and efficacy of CSO as a topical agent to facilitate the healing of wounds in humans. Finally, these findings underscore the safety profile of CSO as a natural product compared to the reference control group. These robust data further support the promising potential of CSO as a safe and viable option for dermal applications, with no adverse effects observed on liver and kidney functions.”

https://www.frontiersin.org/journals/chemistry/articles/10.3389/fchem.2024.1381527/full

Revitalizing polycystic ovary syndrome: The therapeutic impact of low-dose ∆ tetrahydrocannabinol-9 through reduction of oxidative stress and modulation of macrophage polarization

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“Objectives: Polycystic ovary syndrome (PCOS) is a complex metabolic and endocrine disorder associated with chronic inflammation. However, the effect of ∆ tetrahydrocannabinol-9 (THC) on PCOS has not been evaluated. Therefore, this study aimed to investigate the immunomodulatory effects of THC in an animal model of PCOS.

Materials and methods: Twenty female Sprague-Dawley rats, aged 4 weeks, were divided into four groups. The control group received a normal diet, the sham group received a vehicle (carboxymethyl cellulose), the PCOS group received a high-fat diet (HFD) for 16 weeks followed by letrozole for 4 weeks, and the THC group received an HFD for 16 weeks followed by letrozole+THC (0.02 mg/kg) for 4 weeks.

Results: The PCOS animals exhibited significantly higher levels of testosterone, insulin, triglycerides, and total cholesterol, along with elevated inflammatory and oxidative stress markers compared to the control group. Flow cytometry and real-time PCR analysis revealed an increase in M1 macrophage markers and a decrease in M2 macrophage markers compared to the control group. However, the administration of a low dose of THC mitigated these disturbances.

Conclusion: Low-dose THC improved inflammatory responses and shifted the balance of M1/M2 macrophage markers towards M2 macrophages in the animal model of PCOS.”

https://pubmed.ncbi.nlm.nih.gov/38911246/

Hempseed protein-derived short- and medium-chain peptides and their multifunctional properties

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“Nowadays, the growing knowledge about the high nutritional value and potential functionality of hempseeds, the edible fruits of the Cannabis sativa L. plant, has sparked a surge in interest in exploring the worthwhile attributes of hempseed proteins and peptides. This trend aligns with the increasing popularity of hemp-based food, assuming a vital role in the global food chain. This chapter targets the nutritional and chemical composition of hempseed in terms of short- and medium-chain bioactive peptides. The analytical approaches for their characterization and multifunctional properties are summarized in detail. Moreover, the processing, functionality, and application of various hempseed protein products are discussed. In the final part of the chapter-for evaluating their propensity to be transported by intestinal cells-the transepithelial transport of peptides within hempseed protein hydrolysate is highlighted.”

https://pubmed.ncbi.nlm.nih.gov/38906589/

“Cannabis sativa L. is an annual, dioecious plant within the Cannabinaceae family. It has a well-documented history of serving as a source of both food and medicine over the ages.”

https://www.sciencedirect.com/science/article/abs/pii/S1043452624000020?via%3Dihub