Inhibiting Human and Leishmania Arginases Using Cannabis sativa as a Potential Therapy for Cutaneous Leishmaniasis: A Molecular Docking Study

tropicalmed-logo

“Cutaneous leishmaniasis (CL), a vector-borne parasitic disease caused by the Leishmania protozoan, is a serious public health problem in Morocco. The treatment of this disease is still based on pentavalent antimonials as the primary therapy, but these have associated side effects. Thus, the development of effective, risk-free alternative therapeutics based on natural compounds against leishmaniasis is urgent. Arginase, the key enzyme in the polyamine biosynthetic pathway, plays a critical role in leishmaniasis outcome and has emerged as a potential therapeutic target.

The objective of this study was to test Cannabis sativa‘s phytochemical components (cannabinoids and terpenoids) through molecular docking against Leishmania and human arginase enzymes.

Our results showed that delta-9-tetrahydrocannabinol (THC) possessed the best binding energies of -6.02 and -6.35 kcal/mol with active sites of Leishmania and human arginases, respectively. Delta-9-THC interacted with Leishmania arginase through various amino acids including His139 and His 154 and linked to human arginase via His 126. In addition to delta-9-THC, caryophyllene oxide and cannabidiol (CBD) also showed a good inhibition of Leishmania and human arginases, respectively.

Overall, the studied components were found to inhibit both arginases active sites via hydrogen bonds and hydrophobic interactions. These components may serve as therapeutic agents or in co-administrated therapy for leishmaniasis.”

https://pubmed.ncbi.nlm.nih.gov/36548655/

“Since CL is still a public health problem in low-income and developing countries, the discovery of an efficient, less toxic, and accessible therapy is a necessity. The present in silico study was the first to investigate C. sativa’s selected constituents as selective inhibitory agents for parasitic as well as host arginases, which play an important role in this parasitic infection pathology. Interestingly, THC showed a great inhibitory potential for both species’ enzymes and will allow a better control of leishmaniasis.”

https://www.mdpi.com/2414-6366/7/12/400

Cannabis sativa L. alleviates loperamide-induced constipation by modulating the composition of gut microbiota in mice

Frontiers - Crunchbase Company Profile & Funding

“MaZiRenWan (MZRW) is the most frequently used Traditional Chinese Medicine formula to treat chronic constipation, Cannabis sativa L. is regarded as a monarch drug in MZRW. However, the targets of Cannabis sativa L. that enhance colonic motility and improve constipation symptoms remain unknown.

This study was designed to investigate the laxative effect and underlying mechanism of the water extract of Cannabis sativa L. (WECSL) using a loperamide-induced constipation mouse model.

We found that WECSL treatment significantly improved intestinal motility and water-electrolyte metabolism, decreased inflammatory responses, prevented gut barrier damage, and relieved anxiety and depression in constipated mice. WECSL also structurally remodeled the composition of the gut microbiota and altered the abundance of bacteria related to inflammation, specifically Butyricicoccus and Parasutterella. Moreover, WECSL failed to relieve constipation symptoms following intestinal flora depletion, indicating that WECSL alleviates constipation symptoms depending on the gut microbiota.

Our research provides a basis for WECSL to be further investigated in the treatment of constipation from the perspective of modern medicine.”

https://pubmed.ncbi.nlm.nih.gov/36532754/

“In conclusion, this study demonstrated that WECSL can improve constipation symptoms, reduce anxiety and depression behaviors, and inhibit intestinal inflammation. WECSL also structurally remodeled the composition of the gut microbiota, altering the abundance of bacteria related to inflammation.

Our research provides a basis for WECSL to be further investigated in the treatment of constipation from the perspective of modern medicine. Constipation may be prevented and improved by targeting these possible gut bacteria.”

https://www.frontiersin.org/articles/10.3389/fphar.2022.1033069/full


Topical Cannabidiol in the Treatment of Digital Ulcers in Patients with Scleroderma: Comparative Analysis and Literature Review

American Professional Wound Care Association - Advances in Skin & Wound Care

“Objective: To explore the effect of topical cannabidiol (CBD) in treating digital ulcers in patients with systemic sclerosis (SSc).

Methods: In total, 45 patients with SSc who had digital ulcers were consecutively enrolled between January 2019 and December 2019. Of the participants, 25 were treated with CBD during surgical debridement and 20 were treated with standard local therapy. A numeric rating scale for pain and Health Assessment Questionnaire Disability Index were administered at the baseline and at the end of treatment.

Results: Local treatment with CBD was significantly associated with lower pain scores, higher health assessment scores, and an increase in participants’ total hours of sleep. Patients in the control group more frequently required additional analgesic therapy.

Conclusions: Topical CBD may be a valuable tool to treat pain related to digital ulcers in patients with SSc.”

https://pubmed.ncbi.nlm.nih.gov/36537770/

“Topical administration of CBD is a safe, effective, noninvasive tool that is associated with improved wound-related pain, DU healing, and QoL of patients with SSc.”

https://journals.lww.com/aswcjournal/Fulltext/2023/01000/Topical_Cannabidiol_in_the_Treatment_of_Digital.4.aspx

The Modulation of Blue-Light-Induced Inflammation, Intracellular Lipid Secretion, and Oxidative Stress in Sebocytes with Cannabidiol

“Light-induced skin damage leads to cellular or molecular dysfunction, thus potentially causing different skin issues (e.g., skin aging, seborrheic dermatitis and pigmentation). Blue light, a potent visible light that was previously adopted for promoting skin regeneration, draws considerable concerns in the past several years due to their potential damage to the skins. In this work, we investigated the roles of blue light in skewing the functions of sebocytes – the major cells that compose the sebaceous gland – an important “active” neuro-immuno-endocrine organ in maintaining skin functions.

For therapeutically purposes, we employed cannabidiol (CBD), a clinically used non-psychotropic phytocannabinoid, to revert blue-light-induced sebocytes dysfunctions, including intracellular lipid secretion, inflammation, reactive oxygen species (ROS) secretion, and cell cycles. At the cellular level, CBD reduced the blue-light-enhanced intracellular lipid secretion, decreased inflammation, down-regulated intracellular ROS production, and restored the skewed cell cycles in the sebocytes. In the intracellular mechanism, CBD inhibited the blue-light-induced pro-apoptotic activity through rebalance BCL-2/BAX expression and down-regulated the NF-κB p65 pathway.

Collectively, this study demonstrated that CBD was a potent therapeutic agent for maintaining normal sebocytes functions, thus is a promising drug for skincare purposes, especially considering its effectiveness in restoring the twisted sebocytes behaviors.”

https://pubmed.ncbi.nlm.nih.gov/36524438/

https://onlinelibrary.wiley.com/doi/10.1111/php.13764

Receptor-mediated effects of Δ9 -THC & CBD on the inflammatory response of alveolar macrophages

“Δ9 -tetrahydrocannabinol (Δ9 -THC) and cannabidiol (CBD) are cannabinoids found in Cannabis sativa. While research supports cannabinoids reduce inflammation, the consensus surrounding receptor(s) mediated effects has yet to be established.

Here, we investigated the receptor-mediated properties of Δ9 -THC and CBD on alveolar macrophages, an important pulmonary immune cell in direct contact with cannabinoids inhaled by cannabis smokers.

MH-S cells, a mouse alveolar macrophage cell line, were exposed to Δ9 -THC and CBD, with and without lipopolysaccharide (LPS). Outcomes included RNA-sequencing and cytokine analysis. Δ9 -THC and CBD alone did not affect the basal transcriptional response of MH-S cells.

In response to LPS, Δ9 -THC and CBD significantly reduced the expression of numerous pro-inflammatory cytokines including TNF-α, IL-1β and IL-6, an effect that was dependent on CB2 . The anti-inflammatory effects of CBD- but not Δ9 -THC- were mediated through a reduction in signaling through NF-κB and ERK1/2.

These results suggest that CBD and Δ9 -THC have potent immunomodulatory properties in alveolar macrophages, a cell type important in immune homeostasis in the lungs. Further investigation into the effects of cannabinoids on lung immune cells could lead to the identification of therapies that may ameliorate conditions characterized by inflammation.”

https://pubmed.ncbi.nlm.nih.gov/36510483/

https://onlinelibrary.wiley.com/doi/10.1111/imcb.12614


Cannabis sativa Cannabinoids as Functional Ingredients in Snack Foods-Historical and Developmental Aspects

plants-logo

“The published health benefits of Cannabis sativa has caught the attention of health-conscious consumers and the food industry. Historically, seeds have long been utilized as a food source and currently there is an increasing number of edibles on the market that contain cannabis. Cannabinoids include the psychoactive constituent, delta-9-tetrahydrocannabinol (THC), and the non-psychoactive cannabidiol (CBD) that are both compounds of interest in Cannabis sativa.

This paper looks at the distribution of nutrients and phytocannabinoids in low-THC Cannabis sativa, the historical uses of hemp, cannabis edibles, and the possible side-effects and concerns related to cannabis edibles. Several authors have pointed out that even though the use of cannabis edibles is considered safe, it is important to mention their possible side-effects and any concerns related to its consumption that negatively influence consumer acceptance of cannabis edibles. Such risks include unintentional overdose by adults and accidental ingestion by children and adolescents resulting in serious adverse effects. Therefore, cannabis edibles should be specifically packaged and labelled to differentiate them from known similar non-cannabis edibles so that, together with tamperproof packaging, these measures reduce the appeal of these products to children.”

https://pubmed.ncbi.nlm.nih.gov/36501366/

“Cannabis sativa possesses many health-promoting qualities and so it has played an effective role as a traditional medicine to treat a variety of ailments from pain, anxiety and weight gain through to conditions such as cardiovascular disease and diabetes, as well as infectious diseases such as malaria, and cancer.

Opinion regarding cannabis edibles is changing amongst consumers and most countries around the world are shifting towards the legalization of the recreational and medicinal use of cannabis leading to a rapid increase in the global acceptance and availability of cannabis edibles. “

https://www.mdpi.com/2223-7747/11/23/3330


Antibacterial, antioxidant, and haemolytic potential of silver nanoparticles biosynthesized using roots extract of Cannabis sativa plant

Publication Cover

“In this study, Cannabis sativa roots extract has been employed for the biosynthesis of silver nanoparticles (AgNPs). The appearance of reddish-brown colour followed by absorption peak of AgNPs at 408 nm through UV-vis spectrophotometry suggested biosynthesis of AgNPs. The size of the particles ranged from 90-113 nm, confirmed using DLS and TEM along with zeta potential of -25.3 mV. The FTIR provided information regarding the phytochemical capping. The study was further elaborated for determining AgNPs antibacterial, antioxidant, and cellular toxicity using MIC, DPPH, MTT, and haemolytic assays, respectively. The AgNPs were significantly effective against Staphylococcus aureus (Gram-positive), as compared to that of Pseudomonas aeruginosaKlebsiella pneumoniae, and Escherichia coli (Gram-negative). AgNPs also exhibited remarkable antioxidant potential wherein 58.01 ± 0.09% free radical scavenging was observed at a concentration of 100 µg/ml. AgNPs revealed lower cytotoxicity where cell viability was observed to be 52.38 ± 0.6% at a very high concentration of 500 µg/ml in HEK 293 cells. Further, very low toxicity was seen in RBCs i.e. 6.47 ± 0.04% at a high concentration of 200 µg/ml. Thus, the current study beholds anticipation that Cannabis sativa ethanolic root extract-mediated AgNPs may play a vital role in therapeutic.”

https://pubmed.ncbi.nlm.nih.gov/36519372/

“The study demonstrates the efficient biosynthesis of silver nanoparticles using Cannabis sativa ethanolic root extract. The potency of the plant extract and phytochemically fabricated silver nanoparticles were analysed over certain parameters such as antimicrobial, antioxidant and cellular toxicity tests. The study concludes the significant effectiveness of silver nanoparticles, thus prognosticating theirs use henceforth.”

https://www.tandfonline.com/doi/full/10.1080/21691401.2022.2149543

Phytocannabinoids Stimulate Rejuvenation and Prevent Cellular Senescence in Human Dermal Fibroblasts

cells-logo


“In light of the increased popularity of phytocannabinoids (pCBs) and their appearance in beauty products without rigorous research on their rejuvenation efficacy, we decided to investigate the potential role of pCBs in skin rejuvenation.

Utilizing healthy and stress-induced premature senescent (SIPS) CCD-1064Sk skin fibroblasts, the effects of pCBs on cellular viability, functional activity, metabolic function, and nuclear architecture were tested. Both delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) within the range of 0.5 µM to 2.0 µM increased cell growth in a dose-dependent manner while significantly decreasing senescence as measured by beta-galactosidase activity.

Utilizing a scratch assay, both THC and CBD (2.0 µM) significantly improved wound healing in both healthy and SIPS fibroblasts. THC and CBD altered nuclear architecture and mRNA levels of cell cycle regulators and genes involved in ECM production. Subsequently, we found ELN, Cyclin D1, PCNA, and BID protein levels altered by SIPS but ameliorated after pCBs exposure in human dermal fibroblasts.

Lastly, we compared the efficacy of THC and CBD with common anti-aging nutrient signaling regulators in replicative senescent adult human dermal fibroblasts, CCD-1135Sk.

Both THC and CBD were found to improve wound healing better than metformin, rapamycin, and triacetylresveratrol in replicative senescent CCD-1135Sk fibroblasts. Therefore, pCBs can be a valuable source of biologically active substances used in cosmetics, and more studies using clinical trials should be performed to confirm the efficacy of phytocannabinoids.”

https://pubmed.ncbi.nlm.nih.gov/36497198/

“THC and CBD stimulated fibroblasts’ ability to close damaged wounds, while THC induced wound healing better than common nutrient signaling regulators,”

https://www.mdpi.com/2073-4409/11/23/3939

Cannabinoids inhibit ethanol-induced activation of liver toxicity in rats through JNK/ERK/MAPK signaling pathways

“Cannabinoids (CBs) are psychoactive compounds, with reported anticancer, anti-inflammatory, and anti-neoplastic properties. The study was aimed at assessing the hepatoprotective effects of CB against ethanol (EtOH)-induced liver toxicity in rats. The animals were divided into seven groups: control (Group I) and Group II were treated with 50% ethanol (EtOH 5 mg/kg). Groups III, IV, and VI were treated with (EtOH + CB 10 mg/kg), (EtOH + CB 20 mg/kg), and (EtOH + CB 30 mg/kg), respectively. Groups V and VII consisted of animals treated with 20 and 30 mg/kg, of CB, respectively. Biochemical analysis revealed that Group IV (EtOH + CB 20 mg/kg) had reduced levels of ALT-alanine transferase, AST-aspartate aminotransferase, ALP-alanine peroxidase, MDA-malondialdehyde and increased levels of GSH-reduced glutathione. Histopathological analysis of liver and kidney tissues showed that EtOH + CB (20 and 30 mg/kg) treated animal groups exhibited normal tissue architecture similar to that of the control group. ELISA revealed that the inflammatory markers were reduced in the animal groups that were treated with EtOH + CB 20 mg/kg, in comparison to the animals treated only with EtOH. The mRNA expression levels of COX-2, CD-14, and MIP-2 showed a remarkable decrease in EtOH + CB treated animal groups to control groups. Western blot analysis revealed that CB downregulated p38/JNK/ERK thereby exhibiting its hepatoprotective property by inhibiting mitogen-activated protein kinase pathways. Thus, our findings suggest that CB is a potential candidate for the treatment of alcohol-induced hepatotoxicity.”

https://pubmed.ncbi.nlm.nih.gov/36453646/

https://onlinelibrary.wiley.com/doi/10.1002/jbt.23260

Cannabidiol Protects Striatal Neurons by Attenuating Endoplasmic Reticulum Stress

View details for Cannabis and Cannabinoid Research cover image

“Introduction: The aggregation of misfolded proteins in the endoplasmic reticulum (ER) is a pathological trait shared by many neurodegenerative disorders. This aggregation leads to the persistent activation of the unfolded protein response (UPR) and ultimately apoptosis as a result of ER stress. Cannabidiol (CBD) has been demonstrated to be neuroprotective in various cellular and animal models of neurodegeneration, which has been attributed to its antioxidant and anti-inflammatory properties. However, little is known about the role of CBD in the context of protein folding and ER stress. The purpose of this study was to investigate whether CBD is neuroprotective against an in vitro model of ER stress. 

Materials and Methods: Using different exposure models, mouse striatal STHdhQ7/Q7 cells were exposed to either the ER stress inducer thapsigargin (TG) and/or CBD. Cell viabilities assays were used to investigate the effect of CBD pre-treatment, co-treatment, and post-treatment on TG-induced cell death. Real-time quantitative polymerase chain reaction was used to measure changes in ER stress regulators and UPR genes such as glucose-regulated protein-78 (GRP78), mesencephalic astrocyte-derived neurotrophic factor (MANF), B cell lymphoma 2 (BCL-2), BCL-2 interacting mediator of cell death (BIM), and caspase-12. 

Results: Cell viability increased significantly when cells were pre-treated with CBD before TG exposure. An increase in the gene expression of pro-survival ER chaperone GRP78 and ER-resident neurotrophic factor MANF coincided with this effect and decreased ER-mediated pro-apoptotic markers such as BIM, and caspase-12 was observed. 

Conclusions: These data suggest that CBD pre-treatment is neuroprotective against TG-induced cell death. Understanding the role of ER stress in CBD-driven neuroprotection provides insight into the therapeutic potential of CBD and the role of ER dysfunction in neurodegenerative disorders.”

https://pubmed.ncbi.nlm.nih.gov/36454179/

https://www.liebertpub.com/doi/10.1089/can.2022.0090