Cannabis sativa (Hemp) seed-derived peptides WVYY and PSLPA modulate the Nrf2 signaling pathway in human keratinocytes

pubmed logo

“Cannabis sativa (Hemp) seeds are used widely for cosmetic and therapeutic applications, and contain peptides with substantial therapeutic potential.

Two key peptides, WVYY and PSLPA, extracted from hemp seed proteins were the focal points of this study. These peptides have emerged as pivotal contributors to the various biological effects of hemp seed extracts. Consistently, in the present study, the biological effects of WVYY and PSLPA were explored.

We confirmed that both WVYY and PSLPA exert antioxidant and antibacterial effects and promote wound healing.

We hypothesized the involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in these observed effects, given that Nrf2 is reported to be a central player in the regulation of these observed effects. Molecular-level investigations unequivocally confirmed the role of the Nrf2 signaling pathway in the observed effects of WVYY and PSLPA, specifically their antioxidant effects.

Our study highlights the therapeutic potential of hemp seed-derived peptides WVYY and PSLPA, particularly with respect to their antioxidant effects, and provides a nuanced understanding of their effects. Further, our findings can facilitate the investigation of targeted therapeutic applications and also underscore the broader significance of hemp extracts in biological contexts.”

https://pubmed.ncbi.nlm.nih.gov/38781174/

“Although a more in-depth investigation into the precise roles of each peptide is necessary, we believe that a thorough examination of the highly specific roles of various peptides could lead to a broad range of medical and biological applications. In conclusion, we confirmed that the peptides WVYY and PSLPA derived from hemp seed extracts exhibit multiple effects, including antioxidant mechanisms. We propose that the overall “effect” of hemp extract originates from these contributions.”

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0298487

Exploring the versatile roles of the endocannabinoid system and phytocannabinoids in modulating bacterial infections

pubmed logo

“The endocannabinoid system (ECS), initially identified for its role in maintaining homeostasis, particularly in regulating brain function, has evolved into a complex orchestrator influencing various physiological processes beyond its original association with the nervous system. Notably, an expanding body of evidence emphasizes the ECS’s crucial involvement in regulating immune responses.

While the specific role of the ECS in bacterial infections remains under ongoing investigation, compelling indications suggest its active participation in host-pathogen interactions. Incorporating the ECS into the framework of bacterial pathogen infections introduces a layer of complexity to our understanding of its functions.

While some studies propose the potential of cannabinoids to modulate bacterial function and immune responses, the outcomes inherently hinge on the specific infection and cannabinoid under consideration. Moreover, the bidirectional relationship between the ECS and the gut microbiota underscores the intricate interplay among diverse physiological processes.

The ECS extends its influence far beyond its initial discovery, emerging as a promising therapeutic target across a spectrum of medical conditions, encompassing bacterial infections, dysbiosis, and sepsis.

This review comprehensively explores the complex roles of the ECS in the modulation of bacteria, the host’s response to bacterial infections, and the dynamics of the microbiome. Special emphasis is placed on the roles of cannabinoid receptor types 1 and 2, whose signaling intricately influences immune cell function in microbe-host interactions.”

https://pubmed.ncbi.nlm.nih.gov/38775488/

https://journals.asm.org/doi/10.1128/iai.00020-24

In vitro Antibacterial Activity of Ethanolic Tanao Si Kan Dang RD1 (Cannabis sativa L.) Extracts Against Human Antibiotic-Resistant Bacteria

pubmed logo

“Background and Objective: A new strain of cannabis, Cannabis sativa L. Tanao Si Kan Dang RD1, has been approved and registered by the Rajamangala University of Technology Isan, Thailand. The C. sativa is acknowledged for its medicinal properties which demonstrated various therapeutic properties, such as anti-cancer and antibacterial activities. This study aimed to investigate the antibacterial activity of ethanolic extracts from the stems and leaves of the Tanao Si Kan Dang RD1 strain against seven antibiotic-resistant bacteria. 

Materials and Methods: The primary antibacterial activity of ethanolic Tanao Si Kan Dang RD1 extracts were determined using the disc diffusion method, while the minimum inhibitory concentrations (MICs) and minimum bactericidal concentrations (MBCs) were determined using the broth microdilution method. 

Results: The largest inhibition zone, measuring 12 mm, was observed in leaf extracts against Pseudomonas aeruginosa 101. The lowest MIC, at 0.78 mg/mL, was obtained from stem extracts against Stenotrophomonas maltophilia. The lowest MBCs, at 12.5 mg/mL, were observed in leaf extracts against Enterococcus faecalisAcinetobacter baumannii, multidrug-resistant KlebsiellapneumoniaeStenotrophomonas maltophilia and Pseudomonas aeruginosa 101 and stem extracts against Acinetobacter baumannii, multidrug-resistant Klebsiella pneumoniaeStenotrophomonas maltophilia and Pseudomonas aeruginosa 101. 

Conclusion: This study presents a novel finding regarding the antibacterial activity of ethanolic extracts from the leaves and stems of Tanao Si Kan Dang RD1 against antibiotic-resistant bacteria. The potential application of these cannabis plant extracts in the development of antibiotics capable of combating antibiotic-resistant pathogenic bacteria represents a promising strategy to address a significant global health concern.”

https://pubmed.ncbi.nlm.nih.gov/38686733/

https://scialert.net/abstract/?doi=pjbs.2024.119.124

Immunostimulatory and Antibacterial Effects of Cannabis sativa L. Leaves on Broilers

pubmed logo

“The aim of this study was to evaluate the effect of dried Cannabis sativa L. leaves as a phytogenic mixture added to broiler feed on CD4+ and CD8+ T lymphocyte subpopulations,

Newcastle disease virus (NDV) antibody titres, and the presence of E. coli in faecal samples. The study was conducted on 100 male Ross 308 broilers, divided into four groups of 25 broilers, for a 42-day research period. The groups were housed separately in boxes on a litter of softwood shavings and were fed starter mixture from day 1 to day 21 and finisher mixture from day 22 to day 42. Industrial hemp (C. sativa) was grown in the Crkvina area, Croatia (latitude: 45°18’46.8″ N; longitude: 15°31’30″ E). The hemp leaves were manually separated, sun-dried, and ground to a powder. The mixture offered to the control group did not contain cannabis leaves, whereas the three experimental groups received mixtures containing mixed cannabis leaves in a quantity of 10 g/kg, 20 g/kg, or 30 g/kg (E_10, E_20, and E_30, respectively). The mean NDV antibody level was uniform in all study groups until post-vaccination day 14 and increased comparably with time. The percentage of CD4+ and CD8+ lymphocytes in the peripheral blood subpopulation showed statistically significant differences (p < 0.001) in the E_20 group as compared with the control group and both the E_10 and E_30 groups throughout the study period. As the broiler age increased, the CD4+-to-CD8+ ratios also increased and were statistically significant (p < 0.0001) on day 42 in all experimental groups as compared to the control group. Comparing the control group with the experimental groups indicated that the bacterial count was lower in broiler groups having received feed with the addition of 20 g/kg and 30 g/kg C. sativa leaves.

In conclusion, the C. sativa leaves were found to elicit a favourable immunomodulatory effect on cell-mediated and humoral immune responses in broilers via increased CD4+ and CD8+ lymphocyte subpopulations and higher CD4+:CD8+ cell ratios, thus indicating enhanced immune function capacity. In addition, C. sativa leaves may have complementary effects on the broiler post-vaccination immune response, increase broilers’ resistance to infectious diseases, reduce the effect of stress associated with vaccination, and improve broiler health and welfare.”

https://pubmed.ncbi.nlm.nih.gov/38672306/

“Food safety, climate change, the emergence of infectious diseases, the ban on the use of antibiotics as growth promoters, and increasingly demanding intensive production are daily challenges for poultry production. A functional immune system is a prerequisite for animal health, and nutrition is one of the modulators of the immune system; therefore, the appropriate balance of nutrients is extremely important for the proper development and maintenance of the immune system of animals. The antimicrobial and immunomodulatory effects of phytobiotics are properties that make their use important as feed additives for poultry.

Cannabis sativa L. contains many different compounds such as flavonoids, terpenes, and cannabinoids, each with different properties and effects. The effects of C. sativa seeds, essential oils, and cakes as feed additives for poultry have already been investigated, but the effect of C. sativa L. leaves as a feed additive on immunostimulatory and antibacterial activity has not. The results of this study show that C. sativa as a phytogenic additive to animal feed has a favourable antimicrobial and immunomodulatory effect in the production of broiler chickens.”

https://www.mdpi.com/2076-2615/14/8/1159

Antimicrobial, Probiotic, and Immunomodulatory Potential of Cannabis sativa Extract and Delivery Systems

pubmed logo

“The compounds present in hemp show multidirectional biological activity. It is related to the presence of secondary metabolites, mainly cannabinoids, terpenes, and flavonoids, and the synergy of their biological activity. The aim of this study was to assess the activity of the Henola Cannabis sativae extract and its combinations with selected carriers (polyvinyl caprolactam-polyvinyl acetate-polyethylene glycol graft copolymer, magnesium aluminometasilicate, and hydroxypropyl-β-cyclodextrin) in terms of antimicrobial, probiotic, and immunobiological effects.

As a result of the conducted research, the antimicrobial activity of the extract was confirmed in relation to the following microorganisms: Clostridium difficileListeria monocytogenesEnterococcus faecalisStaphylococcus aureusStaphylococcus pyrogenesEscherichia coliKlebsiella pneumoniaeSalmonella typhimuriumPseudomonas aereuginosa, and Candida albicans (microorganism count was reduced from ~102 CFU mL-1 to <10 CFU mL-1 in most cases). Additionally, for the system with hydroxypropyl-β-cyclodextrin, a significant probiotic potential against bacterial strains was established for strains Lactobacillus acidophilusLactobacillus caseiLactobacillus plantarumLactobacillus brevisLactobacillus rhamnosusLactobacillus reuteriPediococcus pentosaceusLactococcus lactisLactobacillus fermentum, and Streptococcus thermophilus (microorganism count was increased from ~102 to 104-107). In terms of immunomodulatory properties, it was determined that the tested extract and the systems caused changes in IL-6, IL-8, and TNF-α levels.”

https://pubmed.ncbi.nlm.nih.gov/38667045/

“This study investigated the antimicrobial potential of Cannabis sativa extract, Henola variety, and systems with carriers. The extract showed antimicrobial activity against pathogenic microorganisms, suggesting its possible application as support in combating infections. Additionally, the system with hydroxypropyl-β-cyclodextrin may possess prebiotic properties, stimulating the growth of probiotic microorganisms. Furthermore, the investigated systems exhibit immunomodulatory and immunostimulatory effects, with potential therapeutic implications for modulating inflammatory responses. Overall, these findings underscore the multifaceted therapeutic potential of Cannabis sativa extracts. The delivery systems might be used as powder-based food additives, but they might also be subjected to formulation studies for the development of an oral dietary supplement.”

https://www.mdpi.com/2079-6382/13/4/369

Antimicrobial and antibiofilm effect of cannabinoids from Cannabis sativa against methicillin-resistant Staphylococcus aureus (MRSA) causing bovine mastitis

pubmed logo

“Antimicrobial resistance (AMR) poses a serious threat to human, animal, and plant health on a global scale. Search and elimination techniques should be used to effectively counter the spread of methicillin-resistant Staphylococcus aureus (MRSA) infections. With only a few novel drugs in clinical development, the quest for plant-based alternatives to prevent the spread of antibiotic resistance among bacteria has accelerated. Treatment of MRSA infections is challenging owing to rapidly emerging resistance mechanisms coupled with their protective biofilms. In the present research, we examined the antibacterial properties of ten plant-derived ethanolic leaf extracts.

The most effective ethanolic leaf extract against MRSA in decreasing order of zone of inhibition, Cannabis sativa L. > Syzygium cumini > Murraya koenigii > Eucalyptus sp. > while Aloe barbadensis, Azadirachta indica, had very little impact. Mangifera indica, Curcuma longa, Tinospora cordifolia, and Carica papaya did not exhibit inhibitory effects against MRSA; hence, Cannabis was selected for further experimental study. The minimal inhibitory concentration (MIC) of Cannabis sativa L. extract was 0.25 mg ml-1 with 86% mortality. At a sub-MIC dosage of 0.125 mg ml-1, the biofilm formation was reduced by 71%.

The two major cannabinoids detected were cannabidiol and delta-9-tetrahydrocannabinol (Δ9-THC), which were majorly attributed to substantial inhibitory action against MRSA. The time-kill kinetics demonstrated a bactericidal action at 4 MIC over an 8-20-h time window with a 90% reduction in growth rate. The results from SEM, and light microscopy Giemsa staining revealed a reduction in cells in the treated group with increased AKP activity, indicating bacterial cell membrane breakdown.

These findings suggested cannabinoids may be a promising alternative to antibiotic therapy for bovine biofilm-associated MRSA.”

https://pubmed.ncbi.nlm.nih.gov/38568425/

https://link.springer.com/article/10.1007/s10123-024-00505-x

Cannabinoids from inflorescences fractions of Trema orientalis (L.) Blume (Cannabaceae) against human pathogenic bacteria

Logo of peerj

“Background

Cannabinoids; tetrahydrocannabinol (THC), cannabidiol (CBD) and cannabinol (CBN), might show antibacterial activity. Trema orientalis is a species in the Cannabaceae that is closely related to Cannabis through plastome phylogenetic evidence. This species is widely distributed throughout tropical Asia and is used as traditional medicine, particularly for the treatment of infectious diseases. However, no studies on the antibacterial activity of cannabinoid-containing inflorescences extracts are available. Thus, the aim of this study was to determine cannabinoid content and antibacterial activity of inflorescences fractions from T. orientalis native to Thailand.

Methods

We hypothesized that inflorescences from T. orientalis might display cannabinoids similar to Cannabis because of their close taxonomic relationship. We extracted the mature inflorescences and infructescence of T. orientalis in three disparate populations from different Thailand floristic regions. Extractions were subsequently partitioned into hydrophilic and lipophilic fractions using distilled water and chloroform. The lipophilic extracts were further fractionated by the column chromatography with gradient elution and analyzed by gas chromatography-mass spectrometry (GC-MS). Characterized cannabinoids were used in bioassays with multidrug-resistance bacteria.

Results

Lipophilic extracts and fractions of inflorescences from all Thailand floristic regions consistently displayed cannabinoids (THC, CBD and CBN) in various quantities. These extracts exhibited inhibitory activity for Staphylococcus aureusPseudomonas aeruginosa, and Acinetobacter baumannii strains with minimum inhibitory concentration values varying from 31.25 to 125 µg/mL.

Conclusion

Our study is the first to report cannabinoid detection in extracts from inflorescences of T. orientalis, a species in the Cannabaceae. These extracts and their fractions containing cannabinoids showed pronounced antibacterial activity. The use of analytic methods also demonstrated reproducible cannabinoid extraction.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8126263/

“Trema orientalis is a pioneer species in the cannabis family (Cannabaceae) that is widely distributed in Thai community forests and forest edges.  T. orientalis can serve as a source of non-toxic natural lipophilic compounds that can be useful as bioactive ingredients in supplement feed development.”

https://pubmed.ncbi.nlm.nih.gov/38282858/

Development of cannabidiol derivatives as potent broad-spectrum antibacterial agents with membrane-disruptive mechanism

pubmed logo

“The emergence of antibiotic resistance has brought a significant burden to public health. Here, we designed and synthesized a series of cannabidiol derivatives by biomimicking the structure and function of cationic antibacterial peptides.

This is the first report on the design of cannabidiol derivatives as broad-spectrum antibacterial agents.

Through the structure-activity relationship (SAR) study, we found a lead compound 23 that killed both Gram-negative and Gram-positive bacteria via a membrane-targeting mechanism of action with low resistance frequencies. Compound 23 also exhibited very weak hemolytic activity, low toxicity toward mammalian cells, and rapid bactericidal properties.

To further validate the membrane action mechanism of compound 23, we performed transcriptomic analysis using RNA-seq, which revealed that treatment with compound 23 altered many cell wall/membrane/envelope biogenesis-related genes in Gram-positive and Gram-negative bacteria. More importantly, compound 23 showed potent in vivo antibacterial efficacy in murine corneal infection models caused by Staphylococcus aureus or Pseudomonas aeruginosa.

These findings would provide a new design idea for the discovery of novel broad-spectrum antibacterial agents to overcome the antibiotic resistance crisis.”

https://pubmed.ncbi.nlm.nih.gov/38266554/

“Natural compounds have been found as an important source of antibiotics. Cannabidiol (CBD), which is derived from the plant cannabis, has a variety of pharmacological activities, including analgesic, anti-inflammatory, anti-epileptic, anti-anxiety, anticonvulsant, anti-cancer, antipsychotic, and antibacterial activities.”

https://www.sciencedirect.com/science/article/abs/pii/S0223523424000291?via%3Dihub

Exploring the Antibacterial Potential of Semisynthetic Phytocannabinoid: Tetrahydrocannabidiol (THCBD) as a Potential Antibacterial Agent against Sensitive and Resistant Strains of Staphylococcus aureus

pubmed logo

“Antimicrobial resistance (AMR) is one of the most challenging problems and is responsible for millions of deaths every year. We therefore urgently require new chemical entities with novel mechanisms of action. Phytocannabinoids have been adequately reported for the antimicrobial effect but not seriously pursued because of either stringent regulatory issues or poor drug-like properties. In this regard, the current work demonstrated the antibacterial potential of tetrahydrocannabidiol (THCBD, 4), a semisynthetic phytocannabinoid, against Staphylococcus aureus, the second-most widespread bug recognized by the WHO. THCBD (4) was generated from cannabidiol and subjected to extensive antibacterial screening. In in vitro studies, THCBD (4) demonstrated a potent MIC of 0.25 μg/mL against Gram-positive bacteria, S. aureus ATCC-29213. It is interesting to note that THCBD (4) has demonstrated strong effectiveness against efflux pump-overexpressing (SA-1199B, SA-K2191, SA-K2192, and Mupr-1) and multidrug-resistant (MRSA-15187) S. aureus strains. THCBD (4) has also shown a good effect in kill kinetic assays against ATCC-29213 and MRSA-15187. In the checkerboard assay, THCBD (4) has shown additive/indifference effects with several well-known clinically used antibiotics, tetracycline, mupirocin, penicillin G, and ciprofloxacin. THCBD (4) also exhibited good permeability in the artificial skin model. Most importantly, THCBD (4) has significantly reduced CFU in mice’s in vivo skin infection models and also demonstrated decent plasma exposure with 16-17% oral bioavailability. Acute dermal toxicity of THCBD (4) suggests no marked treatment-related impact on gross pathophysiology. This attractive in vitro and in vivo profile of plant-based compounds opens a new direction for new-generation antibiotics and warrants further detailed investigation.”

https://pubmed.ncbi.nlm.nih.gov/38051636/

https://pubs.acs.org/doi/10.1021/acsinfecdis.3c00154

Abstract Image

Graphene quantum dots based on cannabis seeds for efficient wound healing in a mouse incisional wound model: Link with stress and neurobehavioral effect

pubmed logo

“Graphene quantum dots (GQDs) are promising biomaterials with potential applicability in several areas due to their many useful and unique features. Among different applications, GQDs are photodynamic therapy agents that generate single oxygen and improve antimicrobial activity. In the present study, and for the first time, GQD were isolated from the Cannabis sativa L. seeds to generate C-GQD as a new biomaterial for antibacterial and wound healing applications. Detailed characterization was performed using FTIR, UV-vis, Raman spectra, photoluminescence, TEM examination, HRTEM, ζ-potential, and XRD. Our results revealed in vitro and in vivo antibacterial activity of C-GQDs against Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli) with reduced minimal inhibitory concentration (MIC) of 236µg/mL for both strains. In addition, the C-GQDs confirmed the in vitro analysis and exhibited anti-inflammatory activity by reducing the level of neutrophils in blood and skin tissue. C-GQDs act by accelerating re-epithelization and granulation tissue formation. In addition, C-GQDs restored neurobehavioral alteration induced by incisional wounds by reducing oxidative stress, decreasing cortisol levels, increasing anxiolytic-like effect, and increasing vertical locomotor activity. The wound-healing effects of C-GQDs support its role as a potential therapeutic agent for diverse skin injuries.”

https://pubmed.ncbi.nlm.nih.gov/38042382/

“In the present work, Cannabis sativa L. seeds GQDs (termed here as C-GQDs) were generated through a novel eco-friendly approach using cannabis seeds as precursor and without the addition of strong oxidants, thus avoiding the production of toxic gases.

Cannabis seeds offer an opportunity in regard to versatility, cost, and availability. They are a rich source of fiber and have significant medicinal value. They contain antibacterial cannabinoids with the potential to kill antibiotic-resistant bacteria. They also possess analgesics and anti-inflammatory effects that can be used in various biomedical applications.

More importantly, we found that C-GQDs accelerate the healing process by killing S. aureus and E. coli implicated in skin wound infection.

The C-GQDs, via their antibacterial, anti-inflammatory, anti-stress, anxiolytic-like effects showed an accelerative potential of wound closure in mice models of incisional wounds.”

https://www.sciencedirect.com/science/article/abs/pii/S0378517323010803?via%3Dihub