scholarly journals In Vitro and Clinical Evaluation of Cannabigerol (CBG) Produced via Yeast Biosynthesis: A Cannabinoid with a Broad Range of Anti-Inflammatory and Skin Health-Boosting Properties

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 491
Author(s):  
Eduardo Perez ◽  
Jose R. Fernandez ◽  
Corey Fitzgerald ◽  
Karl Rouzard ◽  
Masanori Tamura ◽  
...  

Cannabigerol (CBG) is a minor non-psychoactive cannabinoid present in Cannabis sativa L. (C. sativa) at low levels (<1% per dry weight) that serves as the direct precursor to both cannabidiol (CBD) and tetrahydrocannabinol (THC). Consequently, efforts to extract and purify CBG from C. sativa is both challenging and expensive. However, utilizing a novel yeast fermentation technology platform, minor cannabinoids such as CBG can be produced in a more sustainable, cost-effective, and timely process as compared to plant-based production. While CBD has been studied extensively, demonstrating several beneficial skin properties, there are a paucity of studies characterizing the activity of CBG in human skin. Therefore, our aim was to characterize and compare the in vitro activity profile of non-psychoactive CBG and CBD in skin and be the first group to test CBG clinically on human skin. Gene microarray analysis conducted using 3D human skin equivalents demonstrates that CBG regulates more genes than CBD, including several key skin targets. Human dermal fibroblasts (HDFs) and normal human epidermal keratinocytes (NHEKs) were exposed in culture to pro-inflammatory inducers to trigger cytokine production and oxidative stress. Results demonstrate that CBG and CBD reduce reactive oxygen species levels in HDFs better than vitamin C. Moreover, CBG inhibits pro-inflammatory cytokine (Interleukin-1β, -6, -8, tumor necrosis factor α) release from several inflammatory inducers, such as ultraviolet A (UVA), ultraviolet B (UVB), chemical, C. acnes, and in several instances does so more potently than CBD. A 20-subject vehicle-controlled clinical study was performed with 0.1% CBG serum and placebo applied topically for 2 weeks after sodium lauryl sulfate (SLS)-induced irritation. CBG serum showed statistically significant improvement above placebo for transepidermal water loss (TEWL) and reduction in the appearance of redness. Altogether, CBG’s broad range of in vitro and clinical skin health-promoting activities demonstrates its strong potential as a safe, effective ingredient for topical use and suggests there are areas where it may be more effective than CBD.

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Maria del R. Ramos-Jerz ◽  
Socorro Villanueva ◽  
Gerold Jerz ◽  
Peter Winterhalter ◽  
Alexandra M. Deters

Methanolic avocado (Persea americanaMill., Lauraceae) seed extracts were separated by preparative HSCCC. Partition and HSCCC fractions were principally characterized by LC-ESI-MS/MS analysis. Theirin vitroinfluence was investigated on proliferation, differentiation, cell viability, and gene expression on HaCaT and normal human epidermal keratinocytes (NHEK) and normal human dermal fibroblasts (NHDF). The methanol-water partition (M) from avocado seeds and HSCCC fraction 3 (M.3) were mostly composed of chlorogenic acid and its isomers. Both reduced NHDF but enhanced HaCaT keratinocytes proliferation. HSCCC fractionM.2composed of quinic acid among chlorogenic acid and its isomers inhibited proliferation and directly induced differentiation of keratinocytes as observed on gene and protein level. Furthermore,M.2increased NHDF proliferation via upregulation of growth factor receptors. Salidrosides and ABA derivatives present in HSCCC fractionM.6increased NHDF and keratinocyte proliferation that resulted in differentiation. The residual solvent fractionM.7contained among low concentrations of ABA derivatives high amounts of proanthocyanidins B1 and B2 as well as an A-type trimer and stimulated proliferation of normal cells and inhibited the proliferation of immortalized HaCaT keratinocytes.


Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4102
Author(s):  
Avinash S. Mahajan ◽  
Venkata S. Arikatla ◽  
Anita Thyagarajan ◽  
Tetyana Zhelay ◽  
Ravi P. Sahu ◽  
...  

Dermal fibroblasts provide structural support by producing collagen and other structural/support proteins beneath the epidermis. Fibroblasts also produce insulin-like growth factor-1 (IGF-1), which binds to the IGF-1 receptors (IGF-1Rs) on keratinocytes to activate signaling pathways that regulate cell proliferation and cellular responses to genotoxic stressors like ultraviolet B radiation. Our group has determined that the lack of IGF-1 expression due to fibroblast senescence in the dermis of geriatric individuals is correlated with an increased incidence of skin cancer. The present studies tested the hypothesis that pro-energetics creatine monohydrate (Cr) and nicotinamide (NAM) can protect normal dermal human fibroblasts (DHF) against experimentally induced senescence. To that end, we used an experimental model of senescence in which primary DHF are treated with hydrogen peroxide (H2O2) in vitro, with senescence measured by staining for beta-galactosidase activity, p21 protein expression, and senescence associated secretory phenotype cytokine mRNA levels. We also determined the effect of H2O2 on IGF-1 mRNA and protein expression. Our studies indicate that pretreatment with Cr or NAM protects DHF from the H2O2-induced cell senescence. Treatment with pro-energetics post-H2O2 had no effect. Moreover, these agents also inhibited reactive oxygen species generation from H2O2 treatment. These studies suggest a potential strategy for protecting fibroblasts in geriatric skin from undergoing stress-induced senescence, which may maintain IGF-1 levels and therefore limit carcinogenesis in epidermal keratinocytes.


2019 ◽  
Vol 3 (1) ◽  
Author(s):  
Yun Jeong Kim ◽  
Ji Hyun Seok ◽  
Waiting Cheung ◽  
Sung-Nae Lee ◽  
Hyun Hee Jang ◽  
...  

Abstract Background The present study aimed to investigate the anti-inflammatory activity of Helichrysum bracteatum (H. bracteatum) flower extracts in vitro. Methods H. bracteatum flowers were extracted with water, ethanol and 1,3-butylene glycol, and the anti-oxidative activities of the extracts were measured using a 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay. The inhibition of the expression of inflammation-related genes, including tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and cyclooxygenase-2 (COX-2), was evaluated in vitro using reverse transcription-PCR in ultraviolet B (UVB)-irradiated human epidermal keratinocytes (HEKa cells). To investigate the inhibitory effects of H. bracteatum flower extracts on UVB-induced inflammatory responses in HEKa cells, the production of nitric oxide (NO) and TNF-α was measured using enzyme-linked immunosorbent assays. Results were expressed as the mean ± standard deviation; statistical significance was calculated using the Student’s t-test. Results The DPPH assay results showed that H. bracteatum flower extracts have good anti-oxidative effects and inhibited the expression of inflammation-related genes IL-6, COX-2 and TNF-α. Moreover, the production of NO and TNF-α was inhibited by H. bracteatum flower extracts. Conclusions These findings indicate that H. bracteatum flower extracts have efficacy against UVB-induced inflammation-related gene expression.


Cosmetics ◽  
2021 ◽  
Vol 8 (4) ◽  
pp. 110
Author(s):  
José R. Fernández ◽  
Karl Rouzard ◽  
Corey Fitzgerald ◽  
Jason Healy ◽  
Masanori Tamura ◽  
...  

Over the past 15 years, small molecule isoprenylcysteine (IPC) analogs have been identified as a potential new class of topical anti-inflammatories. Clinical studies have demonstrated that IPCs are both safe and effective in promoting healthy skin when applied topically. This work aims to demonstrate N-Succinyl-S-farnesyl-L-cysteine (SFC) as a novel IPC molecule that provides a broad spectrum of benefits for skin. Human promyelocytic cell line HL-60, human dermal microvascular endothelial cells (HDMECs), human dermal fibroblasts (HDFs), and normal human epidermal keratinocytes (NHEKs) were exposed in culture to various inducers to trigger reactive oxygen species, cytokines, or collagenase production. A 49-subject randomized double-blind, vehicle-controlled, split face trial was performed with 1% SFC gel, or 5% niacinamide and vehicle applied for 12 weeks to evaluate anti-wrinkle and anti-aging endpoints. We demonstrated that SFC inhibited GPCR and TLR-induced pro-inflammatory cytokine release in NHEKs and HDMECs from several inflammatory inducers such as UVB, chemicals, cathelicidin, and bacteria. SFC successfully reduced GPCR-induced oxidation in differentiated neutrophils. Moreover, photoaging studies showed that SFC reduced UVA-induced collagenase (pro-MMP-1) production in HDFs. Clinical assessment of 1% SFC gel demonstrated improvement above the vehicle for wrinkle reduction, hydration, texture, and overall appearance of skin. N-Succinyl-S-farnesyl-L-cysteine (SFC) is a novel anti-inflammatory small molecule and is the first farnesyl-cysteine IPC shown to clinically improve appearance and signs of aging, while also having the potential to ameliorate inflammatory skin disorders.


Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2215 ◽  
Author(s):  
Da Kim ◽  
Ji Jang ◽  
Song Jang ◽  
Jungsun Lee

The neuropeptide substance P (SP) is known to stimulate wound healing by regulating the production of relevant cytokines as well as cell proliferation and migration. However, the therapeutic application of SP is limited by its low stability under biological conditions and oxidation during purification, formulation, and storage. To address this problem, we developed a novel formulation of SP as an SP gel, and investigated its wound healing activity both in vitro and in vivo. SP in SP gel was stable at various temperatures for up to 4 weeks. In vitro, SP gel exhibited more potential as a candidate wound-healing agent than SP alone, as evidenced by the observed increases in the proliferation and migration of human epidermal keratinocytes and human dermal fibroblasts. In vivo experiments showed that SP gel treatment enhanced the healing of full-thickness wounds in mice as compared to SP alone. These results demonstrate the benefits of SP gel as a promising topical agent for wound treatment.


2009 ◽  
Vol 17 (2) ◽  
pp. 240-249 ◽  
Author(s):  
Catherine S. Wright ◽  
Maurice A. M. van Steensel ◽  
Malcolm B. Hodgins ◽  
Patricia E. M. Martin

Materials ◽  
2021 ◽  
Vol 14 (3) ◽  
pp. 596
Author(s):  
Anna Czajkowska-Kośnik ◽  
Emilia Szymańska ◽  
Robert Czarnomysy ◽  
Julia Jacyna ◽  
Michał Markuszewski ◽  
...  

Etodolac (ETD), a nonsteroidal anti-inflammatory drug, exhibits antinflammatory, analgesic, and antipyretic activity. The main type of ETD administration is oral route, which is associated with significant systemic side effects. Nanostructured lipid carriers (NLC), a modern lipid formulation, are non-toxic, biocompatible, can improve the solubility and stability of drugs. Nanostructured lipid carriers (NLC) containing etodolac were prepared by a melt-emulsification and ultrasonication technique. Full factorial design (FFD) was applied to optimize the composition of NLC and their properties such as zeta potential, polidyspersity index, and entrapment efficiency. Formulations consisting of Capryol 90, glicerol monostearate, and Tween 20 displayed particle size below 300 nm, encapsulated drug with efficiency of approximately 87% and prolonged drug release up to 24 h. Stable formulations displayed moderately negative surface charge suggesting their limited ability to interact with skin surface but simultaneously presenting their lower risk to cause cell-membrane disruption. In fact, cytotoxicity assessment using human dermal fibroblasts and human epidermal keratinocytes revealed that etodolac-loaded NLC had no important impact on skin cells viability evaluated in vitro, which might evidence that NLC formulations are safe for dermal delivery. The studies developed were relatively fast and simple, requiring no specialized equipment method to prepare NLC as ETD carriers ensuring better solubility and prolonged drug release.


4open ◽  
2021 ◽  
Vol 4 ◽  
pp. 1
Author(s):  
Ayesha Idrees ◽  
Inge Schmitz ◽  
Alice Zoso ◽  
Dierk Gruhn ◽  
Sandra Pacharra ◽  
...  

Nowadays, human skin constructs (HSCs) are required for biomaterials, pharmaceuticals and cosmetics in vitro testing and for the development of complex skin wound therapeutics. In vitro three-dimensional (3D) dermal-epidermal based interfollicular, full-thickness, human skin equivalent (HSE) was here developed, recapitulating skin morphogenesis, epidermal differentiation, ultra-structure, tissue architecture, and barrier function properties of human skin. Different 3D cell culture conditions were tested to optimize HSE maturation, using various commercially available serum/animal component-free and/or fully defined media, and air-liquid interface (ALI) culture. Optimized culture conditions allowed the production of HSE by culturing normal human dermal fibroblasts (NHDFs) for 5–7 days in CELLnTEC-Prime Fibroblast (CnT-PR-F) medium and then culturing normal human epidermal keratinocytes (NHEKs) for 3 days in CELLnTEC-Prime Epithelial culture (CnT-PR) medium on them. Co-culture was then submerged overnight in CELLnTEC-Prime-3D barrier (CnT-PR-3D) medium to stimulate cell-cell contact formation and finally placed at ALI for 15–20 days using CnT-PR-3D medium. Histological analysis revealed uniform distribution of NHDFs in the dermal layer and their typical elongated morphology with filopodia. Epidermal compartment showed a multi-layered structure, consisting of stratum basale, spinosum, granulosum, and corneum. NHDFs and keratinocytes of basal layer were positive for the proliferation marker Kiel 67 (Ki-67) demonstrating their active state of proliferation. The presence of typical epidermal tissue proteins (keratins, laminins, filaggrin, loricin, involucrin, and β-tubulin) at their correct anatomical position was verified by immunohistochemistry (IHC). Moreover, transmission electron microscopy (TEM) analyses revealed basement membrane with lamina lucida, lamina densa, hemidesmosomes and anchoring fibers. The epidermal layers showed abundant intracellular keratin filaments, desmosomes, and tight junction between keratinocytes. Scanning electron microscopy (SEM) analyses showed the interwoven network of collagen fibers with embedded NHDFs and adjacent stratified epidermis up to the stratum corneum similar to native human skin. HSE physiological static contact angle confirmed the barrier function. The developed HSE represents a fundamental in vitro tool to assess biocompatibility of biomaterials, pharmacotoxicity, safety and effectiveness of cosmetics, as well as to investigate skin biology, skin disease pathogenesis, wound healing, and skin infection.


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