bakuchiol and Inflammation

Postinflammatory hyperpigmentation (PIH) occurs following cutaneous injury and is common following resolution of acne especially in patients with skin of color. The objective of this study was to further validate a trichloroacetic acid (TCA)-induced PIH model and compare it to acne-induced PIH using topical bakuchiol, a botanical extract that has been shown to have antimicrobial, anti-inflammatory, antioxidant, and antiacne properties. A prospective, non-randomized clinical trial was conducted on subjects with skin phototypes IV-VI with a history of acne-induced PIH. Subjects applied bakuchiol or vehicle cream twice daily to 2 acne-induced and 2 TCA-induced PIH lesions for 28 days with a third lesion serving as a control in each group. Degree of improvement was defined as the change in the Investigator Global Assessment (IGA) score over 28 days of treatment. Twenty subjects (6 males, 14 females) completed the study. For TCA-induced PIH sites, there was a statistically significant (p < 0.05) degree of improvement with bakuchiol treatment (- 0.50 ± 0.18) compared to vehicle (0.05 ± 0.15) and control (- 0.06 ± 0.17). For acne-induced PIH, there was a greater degree of improvement for bakuchiol (- 1.06 ± 0.23) when compared to vehicle (- 0.56 ± 0.16) and control (- 0.69 ± 0.18); however, statistical significance was not reached (p > 0.05). TCA-induced PIH sites were uniform in size and pigment intensity thereby allowing better comparison among sites. This emphasizes the relevance of using this model for PIH which may help reduce the barriers in clinical trials and help improve access to treatments for patients who suffer from PIH. The results suggest that topical bakuchiol may decrease the severity of PIH.

Topics: Acne Vulgaris; Adolescent; Female; Follow-Up Studies; Humans; Hyperpigmentation; Inflammation; Male; Phenols; Prospective Studies; Severity of Illness Index; Skin; Skin Cream; Skin Pigmentation; Treatment Outcome; Trichloroacetic Acid; Young Adult

Bakuchiol (BAK) has been reported to have a diverse pharmacological property as an antibiotic, anti-cancer, anti-hypolipidemic, anti-inflammatory and anti-convulsant agent. This study aimed to elucidate the immunomodulation and anti-inflammatory mechanism of bakuchiol using lipopolysaccharide stimulated RAW 264.7 macrophages and various animal models. The present study has shown that BAK significantly suppressed the pro-inflammatory cytokine expression in a dose-dependent manner and its oral administration significantly decreased delayed hypersensitivity responses as compared to control group. The assessment of immunomodulatory activity was carried out by the testing Hemagglutinating antibody (HA) titer, delayed type hypersensitivity (DTH) responses and phagocytic index by carbon clearance test. On the other hand, it showed significant decrease in circulating antibody titer and carbon clearance assay in a concentration-dependent manner. BAK has significantly potentiated the cellular immunity as well as humoral immunity by facilitating the footpad thickness responses in sheep RBCs in sensitized mice by significantly decreasing circulating antibody titer. Molecular studies revealed that BAK inhibited the activation of upstream mediator nuclear factor-κB by suppressing the phosphorylation of IκBα and p65. The responses were statistically significant as compared with the control (*p < 0.05, **p < 0.01).

Topics: Animals; Anti-Inflammatory Agents; Cell Proliferation; Cytokines; Disease Models, Animal; Female; Graft Rejection; Hypersensitivity, Delayed; Immunity, Humoral; Immunosuppressive Agents; Inflammation; Inflammation Mediators; Lipopolysaccharides; Lymphocyte Activation; Macrophages; Male; Mice; Mice, Inbred BALB C; NF-kappa B; Phagocytosis; Phenols; Phosphorylation; RAW 264.7 Cells; Sheep; Signal Transduction; Skin Transplantation

Sepsis is a systemic inflammatory reaction that may lead to multiple organ damage and acute lung injury (ALI). Bakuchiol (Bak) has been reported to confer protection against inflammation and oxidative stress. However, its effect on sepsis-induced acute lung injury remains unclear. In the present study, male C57BL/6 mice were subjected to cecal ligation and puncture (CLP), and Bak (15, 30, 60 mg/kg) was administered intragastrically after 0 and 3 h of surgery. Lung water content was detected. Pathologic changes in lung tissues were evaluated via hematoxylin and eosin (H&E) staining. The levels of myeloperoxidase (MPO), IL-1β, IL-6, and TNF-α were evaluated using ELISA. In addition, expression levels of phosphorylated (p)-IκB, ICAM-1, HMGB1, nitrotyrosine (3-NT), claudin-1, and VE-cadherin were detected using Western blot. Further, IL-1β expression was evaluated using immunofluorescence. SOD activity, contents of MDA, and 8-OHdG were detected to determine the level of oxidative stress. Our results suggested that Bak (60 mg/kg) treatment significantly attenuated pathologic changes and edema in lung tissues and attenuated inflammation and oxidative stress in the lung following sepsis. Additionally, Bak treatment alleviated sepsis-induced lung endothelial barrier disruption. In conclusion, Bak treatment attenuates ALI following sepsis by suppressing inflammation, oxidative stress, and endothelial barrier disruption. Our study indicates that Bak is a potential candidate to treat sepsis-induced ALI.

Topics: Acute Lung Injury; Animals; Edema; Endothelium; Inflammation; Lung; Male; Mice; Mice, Inbred C57BL; Oxidative Stress; Phenols; Protective Agents; Sepsis

The bark of the root and stem of Ulmus davidiana var. japonica has been used as a traditional Korean medicine to treat inflammatory disorders. This plant reportedly exhibits antioxidant, anticancer, and anti-inflammatory effects. A search for biologically active compounds in U. davidiana var. japonica extracts yielded bakuchiol, which we structurally identified on the basis of spectral data, including two-dimensional nuclear magnetic resonance spectroscopy and distortionless enhancement by polarization transfer. In our study, bakuchiol (50 microM) inhibited lipopolysaccharide-induced nitric oxide and prostaglandin E(2) production in RAW 264.7 macrophages by 53.7% and 84.2%, respectively. These results suggested that bakuchiol is one of the potent anti-inflammatory components of U. davidiana var. japonica.

Topics: Animals; Anti-Inflammatory Agents; Cell Line, Tumor; Dinoprostone; Inflammation; Mice; Nitric Oxide; Phenols; Plant Bark; Plant Extracts; Plant Roots; Plant Stems; Ulmus

The effects of bakuchiol, a meroterpenoid isolated from the leaves of Psoralea glandulosa L., on phospholipase A2 (PLA2) activity from different sources, human neutrophil responses, zymosan air pouch and topical inflammation in mice, were investigated. This natural product was a weak inhibitor of secretory and intracellular PLA2 but dose-dependently reduced the formation of LTB4 and TXB2 by human neutrophils and platelet microsomes, respectively. In addition, bakuchiol inhibited degranulation in human neutrophils, whereas superoxide generation was not affected. In mice, bakuchiol decreased cell migration, myeloperoxidase activity and eicosanoid levels in the air pouch inflammation induced by zymosan. After topical administration, this compound was effective as an inhibitor of oedema and myeloperoxidase activity in the 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear oedema and significantly reduced the PGE2 content and ear oedema in the arachidonic acid-induced response. Bakuchiol is a natural anti-inflammatory agent able to control leukocytic functions such as eicosanoid production, migration and degranulation in the inflammatory site.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Cell Survival; Dinoprostone; Edema; Humans; In Vitro Techniques; Inflammation; Leukocyte Elastase; Leukocytes; Leukotriene B4; Male; Mice; Neutrophils; Peroxidase; Phenols; Phospholipases A; Phospholipases A2; Superoxides; Thromboxane B2; Zymosan