Development of an Effective Acne Treatment Based on CBD and Herbal Extracts: Preliminary In Vitro, Ex Vivo, and Clinical Evaluation.

Acne vulgaris, the most common form of acne, is characterized by a mixed eruption of inflammatory and noninflammatory skin lesions primarily affecting the face, upper arms, and trunk. The pathogenesis of acne is multifactorial and includes abnormal keratinization and plugging of the hair follicles, increased sebum production, proliferation and activation of Cutibacterium acnes (C. acnes; formerly Propionibacterium acnes, P. acnes), and finally inflammation. Recent studies have found that cannabidiol (CBD) may be beneficial in the treatment of acne. The aim of this study was to explore natural plant extracts that, when combined with CBD, act synergistically to treat acne by targeting different pathogenic factors while minimizing side effects. The first stage of the study investigated the capacity of different plant extracts and plant extract combinations to reduce C. acnes growth and decrease IL-1ß and TNFα secretion from U937 cells. The results found that Centella asiatica triterpene (CAT) extract as well as silymarin (from Silybum marianum fruit extract) had significantly superior anti-inflammatory activity when combined with CBD compared to either ingredient alone. In addition, the CAT extract helped potentiate CBD-induced C. acnes growth inhibition. The three ingredients were integrated into a topical formulation and evaluated in ex vivo human skin organ cultures. The formulation was found to be safe and effective, reducing both IL-6 and IL-8 hypersecretion without hampering epidermal viability. Finally, a preliminary clinical study of this formulation conducted on 30 human subjects showed a statistically significant reduction in acne lesions (mainly inflammatory lesions) and porphyrin levels, thereby establishing a tight correlation between in vitro, ex vivo, and clinical results. Further studies must be conducted to verify the results, including placebo-controlled clinical assessment, to exclude any action of the formulation itself.

DGLA from the Microalga Lobosphaera Incsa P127 Modulates Inflammatory Response, Inhibits iNOS Expression and Alleviates NO Secretion in RAW264.7 Murine Macrophages.

Microalgae have been considered as a renewable source of nutritional, cosmetic and pharmaceutical compounds. The ability to produce health-beneficial long-chain polyunsaturated fatty acids (LC-PUFA) is of high interest. LC-PUFA and their metabolic lipid mediators, modulate key inflammatory pathways in numerous models. In particular, the metabolism of arachidonic acid under inflammatory challenge influences the immune reactivity of macrophages. However, less is known about another omega-6 LC-PUFA, dihomo-γ-linolenic acid (DGLA), which exhibits potent anti-inflammatory activities, which contrast with its delta-5 desaturase product, arachidonic acid (ARA). In this work, we examined whether administrating DGLA would modulate the inflammatory response in the RAW264.7 murine macrophage cell line. DGLA was applied for 24 h in the forms of carboxylic (free) acid, ethyl ester, and ethyl esters obtained from the DGLA-accumulating delta-5 desaturase mutant strain P127 of the green microalga Lobosphaera incisa. DGLA induced a dose-dependent increase in the RAW264.7 cells' basal secretion of the prostaglandin PGE1. Upon bacterial lipopolysaccharide (LPS) stimuli, the enhanced production of pro-inflammatory cytokines, tumor necrosis factor alpha (TNFα) and interleukin 1ß (IL-1ß), was affected little by DGLA, while interleukin 6 (IL-6), nitric oxide, and total reactive oxygen species (ROS) decreased significantly. DGLA administered at 100 µM in all forms attenuated the LPS-induced expression of the key inflammatory genes in a concerted manner, in particular iNOS, IL-6, and LxR, in the form of free acid. PGE1 was the major prostaglandin detected in DGLA-supplemented culture supernatants, whose production prevailed over ARA-derived PGE2 and PGD2, which were less affected by LPS-stimulation compared with the vehicle control. An overall pattern of change indicated DGLA's induced alleviation of the inflammatory state. Finally, our results indicate that microalgae-derived, DGLA-enriched ethyl esters (30%) exhibited similar activities to DGLA ethyl esters, strengthening the potential of this microalga as a potent source of this rare anti-inflammatory fatty acid.

Traditional lifestyles, transition, and implications for healthy aging: An Example from the remote island of Pohnpei, Micronesia.

Lifestyle-related, non-communicable diseases, such as diabetes, hypertension, and obesity have become critical concerns in the Pacific islands of Micronesia. We investigated the relationship between the diminution of traditional lifestyle practices and the decline in the health of the population in the State of Pohnpei, Federated States of Micronesia. To assess this, our interdisciplinary team developed two scales, one to rank individuals on how traditional their lifestyles were and one to rank individuals on the healthiness of their lifestyles. Participants' locations were categorized as living on a remote atoll, living on the main island, or as a transitional population. Pohnpeians living in transitional communities (e.g. recently moved from a remote atoll to the main island, or the reverse) ranked lowest on both the tradition and health scales, rather than ranking intermediate between the remote and main island groups as we had hypothesized. As predicted, individuals residing on the remote atolls were living the most traditional lifestyles and also had the healthiest lifestyles, based on our rating system. The higher an individual scored on the tradition scale, e.g. the more traditional life they lived, the higher they scored on the health scale, suggesting the importance of traditional lifestyle practices for maintaining health. These findings have significant implications for promoting health and longevity of Micronesians and other Pacific Island peoples. We suggest the process of transition be recognized as a significant lifestyle and health risk and be given the attention we give to other risk factors that negatively influence our health. Based on our findings, we discuss and recommend the revitalization of particular traditional lifestyle practices, which may advance healthy aging among Pohnpeians.

Dietary Supplementation With ω6 LC-PUFA-Rich Algae Modulates Zebrafish Immune Function and Improves Resistance to Streptococcal Infection.

Arachidonic acid (ARA, 20:4n-6) and dihomo-γ-linolenic acid (DGLA, 20:3n-6) are omega-6 long-chain polyunsaturated fatty acids (LC-PUFA), which are key precursors for lipid mediators of the immune system and inflammatory response. The microalga Lobosphaera incisa (WT) and its Δ5-desaturase mutant P127 (MUT) are unique photosynthetic sources for ARA and DGLA, respectively. This study explores the effect of dietary supplementation with L. incisa and P127 biomass on tissue fatty acid composition, immune function, and disease resistance in zebrafish (Danio rerio). The broken microalgal biomass was added to commercial fish feed at 7.5 and 15% (w/w), providing 21.8 mg/g feed ARA for the WT-supplemented group and 13.6 mg/g feed DGLA for the MUT-supplemented group at the 15% inclusion levels. An unsupplemented group was used as the control. After 1 month of feeding, fish were challenged with Streptococcus iniae. Fish were sampled before the challenge and 1 week after the challenge for various analyses. Tissue ARA and DGLA levels significantly increased in the liver, corresponding to microalgal supplementation levels. The elevated expression of specific immune-related genes was evident in the kidneys in all treatment groups after 1 month of feeding, including genes related to eicosanoid synthesis, lysozyme, and NF-κB. In the liver, microalgal supplementation led to the upregulation of genes related to immune function and antioxidant defense while the expression of examined genes involved in ARA metabolism was downregulated. Importantly, fish fed with 15% of both WT- and MUT-supplemented feed showed significantly (p < 0.05) higher survival percentages (78 and 68%, respectively, as compared to only 46% in the control group). The elevated expression of genes related to inflammatory and immune responses was evident post-challenge. Collectively, the results of the current study demonstrate the potential of microalgae-derived dietary ARA and DGLA in improving immune competence and resistance to bacterial infection in zebrafish as a model organism.