Antiaging

Synthesis and activity of the salicylic acid ester of bakuchiol in psoriasis-surrogate keratinocytes and skin substitutes

Summary Background Topical retinoids are effective in retarding skin ageing and restoring homeostasis in skin conditions such as psoriasis. However,their adverse effects (AEs), which include irritation (retinoid dermatitis),photosensitivity and teratogenicity, limit their use and patient compliance.Development of retinoid analogues with minimal AEs would allow a broader and more compliant use. Aim To synthesise a novel molecule, bakuchiol salicylate (bakusylan), with a modulatory gene expression profile similar to retinoids, using as reference three prescription retinoids: tretinoin,tazarotene and adapalene. Methods We hypothesized that because bakuchiol salicylate has a structure entirely different from existing retinoids, there would be at least a partial uncoupling of AEs from the skin normalizing activity of this retinoid. This hypothesis was tested at the transcriptional level in psoriatic cytokine-treated cultures of keratinocytes and organotypic skin substitutes, using DNA microarrays and custom PCR arrays. Results Evaluation of the gene expression profile of bakuchiol salicylate revealed elimination of several components of the retinoid-like proinflammatory response and teratogenic signature, without a substantial loss of normalizing potential. A possible mechanism of action, consisting of keratinocyte desensitization to psoriatic cytokine signalling through the inhibition of the signal transducer and regulator of transcription (STAT)1/3/interferon inflammatory signal transduction axis was also identified. Conclusion Bipartite materials obtained by merging two skin-active entities with specific, complementary bioactivities, such as bakuchiol and salicylic acid, may yield a new class of functional retinoids

National Library of Medicine's (NLM)PubMed Central (PMC)Ma, S.; Gobis, K.; Swindell, W. R.;Chaudhuri, R.; Bojanowski, R.;Bojanowski, K.2017-01-04 Clinical and experimental dermatology DOI: 10.1111/ced.13024 ISSN: 0307-6938 Volume: 42 Issue: 3 Pages: 251-260 PMID: 28052368

Antiaging

Melatonin, bakuchiol and ascorbyl tetraisopalmitate synergize to modulate gene expression and restore Hypoxia-Inducible Factor 1 signaling in UV-exposed skin.

Chronic exposure to solar ultraviolet (UV) radiation induces changes to the expression of hundreds of genes in the skin and modulates cellular signaling pathways that alter its structure, function and appearance. To counter these effects, we have developed a 3-in-1 night facial serum (3-in-1 NFS) comprising melatonin, bakuchiol and ascorbyl tetraisopalmitate that is designed to attenuate UV-generated free radicals and support new collagen synthesis. In order to better define its mechanism of action and gain insight into how it might influence the biology of photoaged skin, we performed a transcriptomic analysis of ex vivo skin explants that had been exposed to UV light and treated with 3-in-1 NFS each day for 4 consecutive days. Differentially expressed mRNAs and microRNAs (miRNA) were identified by RNA sequencing and a miRNA interactome was developed. Pathway enrichment analysis was performed to identify pathways likely modulated by 3-in-1 NFS. Our analysis revealed that the combination of active ingredients in 3-in-1 NFS exerted a synergistic effect on skin biology and modulated the expression of genes implicated in the regulation of collagen biosynthesis, angiogenesis, skin barrier function and cellular metabolism. Pathway analysis indicated that these events are driven by Hypoxia-Inducible Factor 1α (HIF-1α) whose expression in UV-exposed skin was partially restored upon 3-in-1 NFS treatment. To our knowledge, 3-in-1 NFS is the first non-drug demonstrated to act upon this pathway in the skin

PubMed Narda, Mridvika; Brown, Anthony;Pérez-Cremades, Daniel; García-Giménez, José Luís; Granger, Corinne 2018-12-31 Cellular and molecular biology (Noisy-le-Grand, France)ISSN: 0145-5680 Volume: 65 Issue: 8 Pages: 39-47 PMID: 32133977

Antiaging

Assessment of a new biological complex efficacy on dysseborrhea,inflammation, and Propionibacterium acnes proliferation

introduction Acne vulgaris is a common chronic inflammatory disease of the pilosebaceous unit triggered by Propionibacterium acnes. A bakuchiol, Ginkgo biloba extract, and mannitol (BGM) complex has been developed to provide patients with acne with a specific dermocosmetic to be used adjunctively with conventional treatments. Objective The aim of these studies was to assess the antibacterial, anti-inflammatory, and antioxidative potential of BGM complex and its individual compounds as well as its impact on sebum composition. Methods The antibacterial, anti-inflammatory, and antioxidative potential of BGM complex and its compounds was assessed through in vitro, ex vivo, and clinical studies. The clinical benefit of BGM complex formulated in a cream was assessed in subjects prone to acne through sebum composition analysis and photometric assessments. Results from the studies showed that the BGM complex has significant antibacterial, anti-inflammatory, and antioxidative properties. At similar concentrations, bakuchiol has up to twice the antioxidative potential than vitamin E. In subjects, BGM complex regulated the sebum composition in acne patients by increasing the level of sapienic and linolenic acid and reducing the level of oleic acid. The reduced number of porphyrins on the skin surface showed that it is also effective against P. acnes. Conclusion BGM complex provides a complete adjunctive care in patients with acne by targeting etiopathogenic factors of acne: dysseborrhea, inflammation, and P. acnes proliferation.

PubMed Central Trompezinski, Sandra; Weber,Sophie; Cadars, Benoît; Larue,Florence; Ardiet, Nathalie;Chavagnac-Bonneville, Marlène;Sayag, Michèle; Jourdan, Eric 2016-08-31 Clinical, Cosmetic and Investigational Dermatology DOI: 10.2147/CCID.S110655 ISSN:1178-7015 Volume: 9 Pages: 233-239 PMID: 27621660

Antiaging Clinical Study

Clinical evidence of the efficacy and safety of a new 3-in-1 anti-aging topical night serum-in-oil containing melatonin, bakuchiol, and ascorbyl tetraisopalmitate: 103 females treated from 28 to 84 days

Topical melatonin is a potent antioxidant, yet there have been few clinical studies on its anti-aging effects on the skin. To clinically assess the anti-aging efficacy and safety of a new 3-in-1 night facial serum (NFS) combining melatonin with bakuchiol, a novel retinol-like ingredient, and ascorbyl tetraisopalmitate, in all skin types. Five clinical studies were performed, with a total of 103 subjects treated from 28 to 84 days. Under dermatologist supervision, a 3-month efficacy and safety study evaluated anti-aging properties by clinical scoring and instrumental evaluations. Two studies evaluated skin hydration properties for 12 hours after a single application of NFS. Two studies were performed in oily skin: a 1-month efficacy and safety study and a 1-month comedogenesis study. After 12 weeks, clinical evaluation showed a statistically significant decrease in wrinkles (11%), an increase in skin firmness (8%), a reduction in redness (70%; P < 0.01 for all), and an overall improvement in skin quality and complexion. The reduction in wrinkles and the increase in skin firmness were also supported by instrumental evaluations (Dermatop and Dynaskin). Hydration levels increased significantly from 30 minutes until 12 hours and transepidermal water loss significantly decreased after 4H and 6H. Subjects favorably evaluated the efficacy and cosmetic properties of the serum, and it was well tolerated in all skin types including oily skin. This 3-in-1 NFS showed significant clinical anti-aging effects when applied once daily and was well tolerated

PubMed Goldberg, David J; Robinson, Deanne Mraz; Granger, Corinne 2019-06-01 Journal of cosmetic dermatology DOI: 10.1111/jocd.12896 ISSN: 1473-2130 Volume: 18 Issue: 3 Pages: 806-814 PMID: 30924254

Antiaging Clinical Study

Efficacy of a Dermocosmetic Serum Combining Bakuchiol and Vanilla Tahitensis Extract to Prevent Skin Photoaging in vitro and to Improve Clinical Outcomes for Naturally Aged Skin

Background Skin aging is characterized by slacking and loss of density, especially under ultraviolet (UV) radiation exposure. Objective To investigate the beneficial effects of a combination containing bakuchiol (BK) and vanilla tahitensis extract (VTE) to prevent skin photoaging in vitro and to improve clinical outcomes for naturally aged skin. Materials and Methods Human dermal fibroblasts were treated with active compounds, exposed to an acute dose of UVA and analyzed by confocal microscopy: actin network for morphology, interleukin-8 (IL-8) for inflammation and p16 for senescence. Human skin was used to evaluate chronic UVA-induced glycosaminoglycan (GAG) loss and to assess the benefit of topical application of a BK+VTE serum (Alcian blue staining). An open-label clinical trial was conducted in women applying the serum twice daily for 56 days (n=43). Skin remodeling was assessed by FaceScan®. Firmness was evaluated through Dynaskin® and clinical scoring. Skin radiance was also rated on standardized full-face photographs. Results UVA induced a significant increase in IL-8 and p16 expression and marked morphological changes in fibroblasts. Treatment with BK or VTE alone prevented both actin network alteration and IL-8 upregulation. Interestingly, BK+VTE demonstrated synergistic protection against IL-8 and p16 overexpression. Serum application prevented GAG loss at the dermo-epidermal junction and increased dermal GAG in UVA-exposed skin explants. In the clinical trial, face ptosis was reduced by 11% on average for 26 responsive subjects and up to 23%. Depth of skin deformation was also reduced by 24% on average for 30 responsive subjects and up to 30%. This firming effect was confirmed by clinical scoring. Radiance was significantly improved by 29% on average for 33 responsive subjects. The serum demonstrated good tolerance/safety. Conclusion BK+VTE combination demonstrated anti-aging efficacy and might provide a substantial benefit in the daily care of naturally aged skin in women, through their synergistic effect on inflammation and senescence.

PubMed Central Noizet, Maïté; Duprat, Laure;Georgescu, Victor; Bessou-Touya,Sandrine; Duplan, Hélène 2020-05-13 Clinical, Cosmetic and Investigational Dermatology DOI: 10.2147/CCID.S235880 ISSN:1178-7015 Volume: 13 Pages: 359-370 PMID: 32494181

Antiaging Clinical study

Bakuchiol: a retinol-like functional compound revealed by gene expression profiling and clinically proven to have anti-aging effects.

The study was undertaken to compare the skin care related activities of retinol and bakuchiol, a potential alternative to retinoids. Retinol is a pivotal regulator of differentiation and growth of developing as well as adult skin. Retinoic acid is the major physiologically active metabolite of retinol regulating gene expression through retinoic acid receptor - dependent and independent pathways. Comparative gene expression profiling of both substances in the EpiDerm FT full thickness skin substitute model was undertaken. Furthermore, type I, III and IV collagens, as well as aquaporin 3 expression was analyzed by ELISA and/or histochemistry in human dermal fibroblasts and/or Epiderm FT skin substitutes. Bakuchiol is a meroterpene phenol abundant in seeds and leaves of the plant Psoralea corylifolia. We present evidence that bakuchiol, having no structural resemblance to retinoids, can function as a functional analogue of retinol. Volcano plots showed great overall similarity of retinol and bakuchiol effects on the gene expression profile. This similarity was confirmed by the side-by-side comparison of the modulation of individual genes, as well as on the protein level by ELISA and histochemistry. Retinol-like functionality was further confirmed for the upregulation of types I and IV collagen in DNA microarray study and also show stimulation of type III collagen in the mature fibroblast model. Bakuchiol was also formulated into a finished skin care product and was tested in clinical case study by twice-a-day facial application. The results showed that, after 12 weeks treatment, significant improvement in lines and wrinkles, pigmentation, elasticity, firmness, and overall reduction in photo-damage was observed, without usual retinol therapy-associated undesirable effects. Based on these data, we propose that bakuchiol can function as an anti-ageing compound through retinol-like regulation of gene expression

PubMed Chaudhuri, RK; Bojanowski, K 2014-06-01 International journal of cosmetic science DOI: 10.1111/ics.12117 ISSN: 0142-5463 Volume: 36 Issue: 3 Pages: 221-30 PMID: 24471735

Antiaging Clinical Study

Clinical Evaluation of a Nature-Based Bakuchiol Anti-Aging Moisturizer for Sensitive Skin.

Patients with sensitive skin find topical retinoid use for anti-aging purposes challenging due to irritation. Bakuchiol, a meroterpene from the Psoralea corylifolia seed, has retinol functionality through retinol-like regulation of gene expression. This research examined the tolerability, efficacy, and barrier effects of a nature-based bakuchiol-containing cleanser and moisturizer in subjects with sensitive skin. 60 female subjects Fitzpatrick skin types I–V age 40–65 years with sensitive mild to moderate photodamaged skin were enrolled in this 4-week study. A sensitive skin panel was constructed: 1/3 eczema/atopic dermatitis, 1/3 rosacea, 1/3 cosmetic intolerance syndrome. Subjects used a nature-based cleanser and moisturizer twice daily and underwent trans epidermal water loss (TEWL), corneometry, tolerability assessments, and efficacy assessments at baseline, 5–10 minutes post-application, and week 4. The skin care products were well tolerated and efficacious (P<0.001) in terms of investigator assessed improvement in visual smoothness, tactile smoothness, clarity, radiance, overall appearance, and global anti-aging. Cheek corneometry measurements demonstrated a statistically significant 16% increase in skin moisture content (P<0.001). A bakuchiol nature-based anti-aging moisturizer is well tolerated and effective in individuals with sensitive skin. J Drugs Dermatol. 2020;19(12): doi:10.36849/JDD.2020.5522

PubMed Draelos, Zoe Diana; Gunt, Hemali;Zeichner, Joshua; Levy, Stanley 2020-12-01 Journal of drugs in dermatology: JDD DOI: 10.36849/JDD.2020.5522 ISSN:1545-9616 Volume: 19 Issue: 12 Pages: 1181-1183 PMID: 33346506

Antiaging Clinical Study

A Clinical Study Evaluating the Efficacy of Topical Bakuchiol (UP256) Cream on Facial Acne.

Acne vulgaris is a common skin disease that manifests clinically as comedones, papules, nodules, and cysts. In this single center, open-label pilot study (ISRCTN13992386), we aimed to evaluate the effectiveness of UP256 cream, a newly patented topical product containing 0.5% bakuchiol, on facial acne and acne-related post-inflammatory hyperpigmentation (PIH). A series of 13 subjects enriched for Fitzpatrick skin types III–VI with mild or moderate acne received treatment with UP256 twice daily for 12 weeks. Efficacy assessments included changes in inflammatory and non-inflammatory lesions as well as a reduction in Evaluator Global Severity Score (EGSS) assessments of acne severity and PIH. Safety, adverse events, and cutaneous tolerability were evaluated throughout the study. UP256 significantly reduced the number of inflammatory lesions and improved existing PIH. UP256 was also cosmetically acceptable and well tolerated by all study subjects. Overall, our results demonstrate that monotherapy with UP256 improves mild to moderate acne and may be particularly well suited for individuals with skin of color.

PubMed Brownell, Lidia; Geen, Susan; E,Yaping; Lee, Wei-Li 2021-03-01 Journal of drugs in dermatology: JDD DOI: 10.36849/JDD.5655 ISSN: 1545-9616 Volume: 20 Issue: 3 Pages: 307-310 PMID: 33683079

Antiaging Clinical Study

Prospective, randomized, double-blind assessment of topical bakuchiol and retinol for facial photoageing

Background:Bakuchiol is a phytochemical that has demonstrated cutaneous antiageing effects when applied topically. Early studies have suggested that bakuchiol is a functional analogue of topical retinoids, as both compounds have been shown to induce similar gene expression in the skin and lead to improvement of cutaneous photodamage. No in vivo studies have compared the two compounds for efficacy and side-effects.

Objectives:To compare the clinical efficacy and side-effect profiles of bakuchiol and retinol in improving common signs of cutaneous facial ageing.

Methods:This was a randomized, double-blind, 12-week study in which 44 patients were asked to apply either bakuchiol 0·5% cream twice daily or retinol 0·5% cream daily. A facial photograph and analytical system was used to obtain and analyse high-resolution photographs of patients at 0, 4, 8 and 12 weeks. Patients also completed tolerability assessment questions to review side-effects. During study visits, a board-certified dermatologist, blinded to study group assignments, graded pigmentation and redness.

Results:Bakuchiol and retinol both significantly decreased wrinkle surface area and hyperpigmentation, with no statistical difference between the compounds. The retinol users reported more facial skin scaling and stinging.

Conclusions:Our study demonstrates that bakuchiol is comparable with retinol in its ability to improve photoageing and is better tolerated than retinol. Bakuchiol is promising as a more tolerable alternative to retinol.

Br J Dermatol 2019; 180:253–254.

Antiaging Clinical Study

Epidermal and Dermal Hallmarks of Photoaging are Prevented by Treatment with Night Serum Containing Melatonin, Bakuchiol, and Ascorbyl Tetraisopalmitate: In Vitro and Ex Vivo Studies

Introduction:Photoaging is a complex process that is chiefly the result of oxidative stress caused by ultraviolet (UV)-generated reactive oxygen species. To counter this process, we developed a 3-in-1 night facial serum (3-in-1 NFS) containing a combination of direct and indirect antioxidants and polyphenols that is designed to attenuate UV-generated free radicals and stimulate dermal protein synthesis. In clinical trials 3-in-1 NFS improved the appearance of photoaged skin. In this study we sought to identify some of the main histologic changes responsible for this.

Methods:We performed an immunolabeling analysis of some of the salient epidermal and dermal proteins in 3-in-1 NFS-treated primary epidermal keratinocytes (HEKs) and dermal fibroblasts (HDFs) in vitro, and in UV-exposed skin explants ex vivo. Numbers of apoptotic sunburn cells following exposure of 3-in-1 NFS-treated skin explants to UV radiation were also determined.

Results:We demonstrate that 3-in-1 NFS increases levels of filaggrin and aquaporin 3 in HEKs, and levels of collagen I and collagen III in HDFs in vitro. Levels of precursor procollagen type I and tropoelastin were increased in ex vivo skin explants. Numbers of apoptotic sunburn cells were significantly reduced in UV-exposed skin explants. These effects were only observed with the combination of ingredients in 3-in-1 NFS, suggesting that they have a synergistic effect on photoaged skin biology.

Conclusion:Our results show that some of the histological hallmarks of photoaging are improved with the use of 3-in-1 NFS.

Keywords:Antioxidant; Ascorbyl tetraisopalmitate; Bakuchiol; Melatonin; Photoaging; Polyphenol; Skin aging; Ultraviolet.

Dermatol Ther (Heidelb) (2020) 10:191–202
https://doi.org/10.1007/s13555-019-00349-8

Antiaging Clinical Study

A dermocosmetic containing bakuchiol, Ginkgo biloba extract and mannitol improves the efficacy of adapalene in patients with acne vulgaris: result from a controlled randomized trial

Background: Acne vulgaris is an inflammatory disorder of the pilosebaceous unit.

Aim: To confirm that BGM (bakuchiol, Ginkgo biloba extract, and mannitol) complex increases the established clinical efficacy of adapalene 0.1% gel in patients with acne.

Methods: A clinical trial was conducted in acne patients. A total of 111 subjects received adapalene 0.1% gel and BGM complex or vehicle cream for 2 months. Assessments comprised Investigator Global Assessment (IGA), global efficacy, seborrhea intensity, inflammatory and non-inflammatory lesions, and subject perception, as well as overall safety and local tolerance and quality of life.

Results: At the end of the trial, inflammatory and non-inflammatory lesions, IGA, global efficacy, and seborrhea intensity had significantly improved in both treatment groups. Differences were statistically significant (P<0.05) in favor of BGM complex for inflammatory lesions as well as IGA and seborrhea intensity. Global efficacy assessments and subject perception confirmed the superiority of BGM complex-including treatment over the comparative combination. Quality of life had improved more with the active combination than with the vehicle combination. In the active group, four subjects had to interrupt temporarily BGM complex and 12 adapalene compared to seven subjects interrupting the vehicle and eleven adapalene in the vehicle group. One subject withdrew from the trial due to an allergy to adapalene. The majority of all events were mild.

Conclusion: BGM complex improves the treatment outcome of adapalene 0.1% gel in patients with acne vulgaris. Overall, safety and local tolerance of BGM complex were good.

Keywords: BGM complex; P. acnes; acne vulgaris; adapalene; bakuchiol; sebum

Clinical, Cosmetic and Investigational Dermatology

Antioxidant

Bakuchiol from Psoralea corylifolia L. Ameliorates acute kidney injury and improves survival in experimental polymicrobial sepsis.

Bakuchiol (BAK) is a prenylated phenolic mono-terpene extracted from the fruit of Psoralea corylifolia L., which exerts a protective effect on organs. However, whether BAK has a protective effect on sepsis-induced acute kidney injury (S-AKI) is not clear. In our study we have demonstrated for the first time that pretreatment with BAK significantly reduced bacterial load, inflammation, and renal oxidative stress in caecal ligation and puncture (CLP)-induced sepsis. Moreover, CLP-induced renal histological damage, mortality and clinical signs were markedly attenuated by BAK. Additionally, BAK inhibited sepsis-induced activation of NF-κB and p38 MAPK signaling in the kidneys. The evidence presented here has confirmed that BAK exerts multifunctional activity in protection against S-AKI. This action of BAK is probably due to the blockade of the NF-κB and p38 MAPK signaling pathways. Our findings offer a novel potential for BAK in protection against sepsis and S-AKI.

PubMed Wang, Jiazheng; Luo, Min; Shen,Jiafan; Liu, Zhiwen; Chen, Ying; Luo,Jie; Zeng, Zhiying; Deng, Dinling;Xiao, Ji 2020-12-01 International immunopharmacology DOI: 10.1016/j.intimp.2020.107000 ISSN: 1567-5769 Volume: 89 Issue: Pt A Pages: 107000 PMID: 33039956

Antioxidant

Antioxidant activity of bakuchiol: experimental evidence and theoretical treatments on the possible involvement of the terpenoid chain.

The protective activity of the plant-derived meroterpene, bakuchiol [1-(4-hydroxyphenyl)-3,7-dimethyl-3-vinyl-1,6-octadiene, 1], against oxidative damages to lipids and proteins has been investigated and rationalized based on the scavenging activity of 1 against various oxidizing radicals (Cl(3)CO(2)(*), linoleic acid peroxyl radicals, LOO(*), DPPH radicals, (*)OH, and glutathiyl radicals). The rate constants of the scavenging reactions, transients formed in these reactions, and their mechanistic pathways have been probed using optical pulse radiolysis technique. Besides 1, its methyl ether derivative 2 also could prevent lipid peroxidation in rat brain homogenate, indicating the probable participation of their terpenoid chains in scavenging LOO(*). This was further corroborated from the pulse radiolytic studies on the reaction between the glutathiyl radicals and the compounds 1 and 2 as well as two other congeners, 3 and 4, which showed transient absorptions at approximately 300 nm attributable to some C-centered allylic radicals. Based on the strong signals at approximately 300 nm with 1-3 as compared to compound 4, formation of the allylic radical adjacent to the trisubstituted olefin function in 1-3 was envisaged. This was confirmed by quantum chemical calculations of the relative energies of the probable radical species derivable from 2 using Hartree-Fock and density functional theory along with self-consistent reaction field model. In the case of 1, the allylic radical was found to be transformed into the phenoxyl radical at a later stage. All these data revealed, for the first time, the importance of the terpenoid moiety of bakuchiol in controlling its antioxidant action via radical scavenging

PubMed Adhikari, S; Joshi, R; Patro, B S;Ghanty, T K; Chintalwar, G J; Sharma,A; Chattopadhyay, S; Mukherjee, T2003-09-01 Chemical research in toxicology DOI: 10.1021/tx034082r ISSN: 0893-228X Volume: 16 Issue: 9 Pages:1062-9 PMID: 12971793

Antioxidant

Bakuchiol Attenuates Oxidative Stress and Neuron Damage by Regulating Trx1/TXNIP and the Phosphorylation of AMPK After Subarachnoid Hemorrhage in Mice.

Subarachnoid hemorrhage (SAH) is a fatal cerebrovascular condition with complex pathophysiology that reduces brain perfusion and causes cerebral functional impairments. An increasing number of studies indicate that early brain injury (EBI), which occurs within the first 72 h of SAH, plays a crucial role in the poor prognosis of SAH. Bakuchiol (Bak) has been demonstrated to have multiorgan protective effects owing to its antioxidative and anti-inflammatory properties. The present study was designed to investigate the effects of Bak on EBI after SAH and its underlying mechanisms. In this study, 428 adult male C57BL/6J mice weighing 20 to 25 g were observed to investigate the effects of Bak administration in an SAH animal model. The neurological function and brain edema were assessed. Content of MDA/3-NT/8-OHdG/superoxide anion and the activity of SOD and GSH-Px were tested. The function of the blood-brain barrier (BBB) and the protein levels of claudin-5, occludin, zonula occludens-1, and matrix metalloproteinase-9 were observed. TUNEL staining and Fluoro-Jade C staining were conducted to evaluate the death of neurons. Ultrastructural changes of the neurons were observed under the transmission electron microscope. Finally, the roles of Trx, TXNIP, and AMPK in the protective effect of Bak were investigated. The data showed that Bak administration 1) increased the survival rate and alleviated neurological functional deficits; 2) alleviated BBB disruption and brain edema; 3) attenuated oxidative stress by reducing reactive oxygen species, MDA, 3-NT, 8-OHdG, gp91phox, and 4-HNE; increased the activities of SOD and GSH-Px; and alleviated the damage to the ultrastructure of mitochondria; 4) inhibited cellular apoptosis by regulating the protein levels of Bcl-2, Bax, and cleaved caspase-3; and 5) upregulated the protein levels of Trx1 as well as the phosphorylation of AMPK and downregulated the protein levels of TXNIP. Moreover, the protective effects of Bak were partially reversed by PX-12 and compound C. To summarize, Bak attenuates EBI after SAH by alleviating BBB disruption, oxidative stress, and apoptosis via regulating Trx1/TXNIP expression and the phosphorylation of AMPK. Its powerful protective effects might make Bak a promising novel drug for the treatment of EBI after SAH

PubMed Central Liu, Haixiao; Guo, Wei; Guo, Hao; Zhao, Lei; Yue, Liang; Li, Xia; Feng,Dayun; Luo, Jianing; Wu, Xun; Cui,Wenxing; Qu, Yan 2020-05-15 Frontiers in PharmacologyDOI: 10.3389/fphar.2020.00712 ISSN: 1663-9812 Volume: 11 PMID:32499702

Antioxidant

Bakuchiol Alleviates Hyperglycemia-Induced Diabetic Cardiomyopathy by Reducing Myocardial Oxidative Stress via Activating the SIRT1/Nrf2 Signaling Pathway.

Bakuchiol (BAK), a monoterpene phenol reported to have exerted a variety of pharmacological effects, has been related to multiple diseases, including myocardial ischemia reperfusion injury, pressure overload-induced cardiac hypertrophy, diabetes, liver fibrosis, and cancer. However, the effects of BAK on hyperglycemia-caused diabetic cardiomyopathy and its underlying mechanisms remain unclear. In this study, streptozotocin-induced mouse model and high-glucose-treated cell model were conducted to investigate the protective roles of BAK on diabetic cardiomyopathy, in either the presence or absence of SIRT1-specific inhibitor EX527, SIRT1 siRNA, or Nrf2 siRNA. Our data demonstrated for the first time that BAK could significantly abate diabetic cardiomyopathy by alleviating the cardiac dysfunction, ameliorating the myocardial fibrosis, mitigating the cardiac hypertrophy, and reducing the cardiomyocyte apoptosis. Furthermore, BAK achieved its antifibrotic and antihypertrophic actions by inhibiting the TGF-β1/Smad3 pathway, as well as decreasing the expressions of fibrosis- and hypertrophy-related markers. Intriguingly, these above effects of BAK were largely attributed to the remarkable activation of SIRT1/Nrf2 signaling, which eventually strengthened cardiac antioxidative capacity by elevating the antioxidant production and reducing the reactive oxygen species generation. However, all the beneficial results were markedly abolished with the administration of EX527, SIRT1 siRNA, or Nrf2 siRNA. In summary, these novel findings indicate that BAK exhibits its therapeutic properties against hyperglycemia-caused diabetic cardiomyopathy by attenuating myocardial oxidative damage via activating the SIRT1/Nrf2 signaling

PubMed Central Ma, Wenshuai; Guo, Wangang;Shang, Fujun; Li, Yan; Li, Wei; Liu, Jing; Ma, Chao 2020-09-30 Oxidative Medicine and Cellular Longevity DOI: 10.1155/2020/3732718 ISSN:1942-0900 Volume: 2020 PMID:33062139

Antioxidant

Bakuchiol: A newly discovered warrior against organ damage.

Bakuchiol (BAK), [(1E,3S)-3-ethenyl-3,7-dimethyl-1,6-octadien-1-yl] phenol is a prenylated phenolic monoterpene extracted from the fruit of Psoralea corylifolia L., which belongs to the Leguminosae plant family. Previous research has shown that BAK exerts a variety of pharmacological effects, including antioxidant, antibacterial, anti-inflammatory, antiaging and estrogen-like effects. In addition, recent studies have indicated that BAK exerts protective effects in the heart, liver, skin and other organs. BAK treatment protects the heart against ischemia-reperfusion injury through modulating cardioprotective pathways. BAK also inhibits liver fibrosis via promoting myofibroblast apoptosis and relieves the hepatotoxicity of multiple toxicants by suppressing oxidative stress and inflammatory changes. BAK inhibits the proliferation of various cancer cells, including stomach, breast and skin cancer cells, thereby exerting anticancer effects. Further, BAK effectively slows skin aging by preserving skin collagen. BAK treatment can protect against bone loss and delay osteoporosis by exerting estrogen-like effects. In addition, BAK remarkably reduces blood glucose and triglycerides and might be a potential pharmacological agent that can be used to protect against pancreatic beta-cell damage and diabetes progression. In this review, the pharmacological mechanisms and protective effects of BAK in human diseases are discussed, with a focus on the protective effects of BAK in the heart, liver and other important organs

PubMed Xin, Zhenlong; Wu, Xue; Ji, Ting; Xu,Baoping; Han, Yuehu; Sun, Meng;Jiang, Shuai; Li, Tian; Hu, Wei; Deng,Chao; Yang, Yang 2019-03-01 Pharmacological research DOI: 10.1016/j.phrs.2019.01.001 ISSN: 1043-6618 Volume: 141 Pages:208-213 PMID: 30610961

Antioxidant

Bakuchiol Protects Against Acute Lung Injury in Septic Mice.

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.

PubMed Zhang, Xinxin; Chang, Ning; Zhang,Yong; Ye, Mingxiang; Han, Zhiping; Li,Jie; Zhang, Jian 2017-04-01 Inflammation DOI: 10.1007/s10753-016-0481-5 ISSN: 0360-3997 Volume: 40 Issue: 2 Pages: 351-359 PMID: 27878684

Antioxidant

Bakuchiol Contributes to the Hepatotoxicity of Psoralea corylifolia in Rats.

Psoralea corylifolia L. (Fructus Psoraleae) is widely used in Asia, but there are concerns about hepatotoxicity caused by constituents such as psoralens and bakukiol. Bakuchiol (BAK) has anti-inflammatory, antipyretic, antibacterial antiviral, anticancer, and estrogenic activity but appears to be hepatotoxic in in vitro tests. This study investigated the hepatotoxicity in vivo in rats. Using intragastrically administered bakuchiol at doses of 52.5 and 262.5 mg/kg for 6 weeks. Bodyweight, relative liver weight, biochemical indicators, histopathology, mRNA expression of CYP7A1, HMG-CoA reductase, BSEP, PPARα, SREBP-2, and MRP3 were measured. Many abnormalities were observed in the bakuchiol-treated groups including suppression of weight gain and food intake, change of some parameters in serum biochemistry, and increased weight of liver. The mRNA expression of CYP7A1, HMG-CoA reductase, PPARα, and SREBP-2 decreased in bakuchiol-treated group, the expression of BSEP increased in bakuchiol-treated low dosage, and the expression of BSEP decreased in bakuchiol-treated high dosage. In conclusion, we provide evidence for the first time that bakuchiol can induce cholestatic hepatotoxicity, suggesting potential hepatotoxicity. The mechanism may be related to effects on liver lipid metabolism, but further investigation is necessary.

PubMed Li, Zhi-Jian; Abulizi, Abudumijiti;Zhao, Guo-Lin; Wang, Tao; Zhou,Fan; Jiang, Zhen-Zhou; Aibai, Silafu;Zhang, Lu-Yong 2017-08-01 Phytotherapy research :PTR DOI: 10.1002/ptr.5851 ISSN: 0951-418X Volume: 31 Issue: 8 Pages:1265-1272 PMID: 28639266

Antioxidant

Bakuchiol augments MyoD activation leading to enhanced myoblast differentiation.

Myoblast differentiation is fundamental to skeletal muscle development and regeneration after injury and defects in this process are implicated in muscle atrophy associated with aging or pathological conditions. MyoD family transcription factors function as mater regulators in induction of muscle-specific genes during myoblast differentiation. We have identified bakuchiol, a prenylated phenolic monoterpene, as an inducer of MyoD-mediated transcription and myogenic differentiation. C2C12 myoblasts treated with bakuchiol exhibit enhanced muscle-specific gene expression and myotube formation. A key promyogenic kinase p38MAPK is activated dramatically by bakuchiol which in turn induced the formation of MyoD/E protein active transcription complexes. Consistently, the recruitment of MyoD and Baf60c to the Myogenin promoter is enhanced in bakuchiol-treated myoblasts. Furthermore, bakuchiol rescues defective p38MAPK activation and myogenic differentiation caused by Cdo-depletion or in RD rhabdomyosarcoma cells. Taken together, these results indicate that bakuchiol enhances myogenic differentiation through p38MAPK and MyoD activation. Thus, bakuchiol can be developed into a potential agent to improve muscular regeneration and repair to treat muscular atrophy

PubMed Lee, Sang-Jin; Yoo, Miran; Go, Ga-Yeon; Kim, Do Hee; Choi, Hyunmo;Leem, Young-Eun; Kim, Yong Kee; Seo, Dong-Wan; Ryu, Jae-Ha; Kang,Jong-Sun; Bae, Gyu-Un 2016-03-25 Chemico-biological interactions DOI: 10.1016/j.cbi.2016.02.008 ISSN:0009-2797 Volume: 248 Pages: 60-7PMID: 26902638

Antioxidant

Bakuchiol protects against pathological cardiac hypertrophy by blocking NF-κB signaling pathway

Bakuchiol (Bak), a monoterpene phenol isolated from the seeds of Psoralea corylifolia, has been widely used to treat a large variety of diseases in both Indian and Chinese folkloric medicine. However, the effects of Bak on cardiac hypertrophy remain unclear. Therefore, the present study was designed to determine whether Bak could alleviate cardiac hypertrophy. Mice were subjected to aortic banding (AB) to induce cardiac hypertrophy model. Bak of 1 ml/100 g body weight was given by oral gavage once a day from 1 to 8 weeks after surgery. Our data demonstrated for the first time that Bak could attenuate pressure overload-induced cardiac hypertrophy and could attenuate fibrosis and the inflammatory response induced by AB. The results further revealed that the effect of Bak on cardiac hypertrophy was mediated by blocking the activation of the NF-κB signaling pathway. In vitro studies performed in neonatal rat cardiomyocytes further proved that the protective effect of Bak on cardiac hypertrophy is largely dependent on the NF-κB pathway. Based on our results, Bak shows profound potential for its application in the treatment of pathological cardiac hypertrophy, and we believe that Bak may be a promising therapeutic candidate to treat cardiac hypertrophy and heart failure.

PubMed Central Wang, Zheng; Gao, Lu; Xiao, Lili;Kong, Lingyao; Shi, Huiting; Tian,Xinyu; Zhao, Luosha 2018-10-31 Bioscience Reports DOI: 10.1042/BSR20181043 ISSN:0144-8463 Volume: 38 Issue: 5PMID: 30242058

Antioxidant

Characterization of glutathione conjugates derived from reactive metabolites of bakuchiol.

Bakuchiol belongs to a family of monoterpene phenols occurring in plant Psoralea corylifolia L., a traditional herbal medicine. Bakuchiol has also demonstrated multiple pharmacologic activities. However, metabolism of bakuchiol had never been investigated. The major objective of the present study was to study the metabolic pathways of bakuchiol in order to identify potential reactive metabolites. A total of five glutathione (GSH) conjugates (M1-M5) were detected in rat/human liver microsomes containing NADPH, GSH, and bakuchiol. M1 and M2 resulted from GSH conjugated on the phenol ring. M3, M4, and M5 were derived from GSH adducted on the side chain. The results displayed that bakuchiol can be bioactivated by oxidation of the phenol moiety to the corresponding ortho-quinone and by epoxidation of the aliphatic side chain to epoxide metabolites. No bakuchiol-derived GSH conjugates were detected in urine of rats given bakuchiol, but six corresponding cysteinylglycine (Cys-Gly) conjugates and mercapturic acids were observed instead. A 2'-iodoxybenzoic acid-mediated oxidation reaction of bakuchiol in the presence of GSH produced M1 and M2, and m-chloroperoxybenzoicacid-mediated oxidation of bakuchiol trapped with GSH generated M3 and M4. The four synthetic metabolites were detected in microsomal incubations. In addition, recombinant P450 enzyme incubations showed that CYP 1A2 was the predominant P450 responsible for the metabolism of bakuchiol. In summary, our results demonstrated that bakuchiol can be bioactivated to quinone and epoxide metabolites. These findings facilitate the understanding of the mechanisms of bakuchiol-induced cytotoxicity.

PubMed Chi, Meina; Peng, Ying; Zheng, Jiang 2016-01-25 Chemico-biological interactions DOI: 10.1016/j.cbi.2015.12.009 ISSN:0009-2797 Volume: 244 Pages: 178-86 PMID: 26712081

Antioxidant

Bakuchiol attenuates myocardial ischemia reperfusion injury by maintaining mitochondrial function: the role of silent information regulator 1.

Ischemia reperfusion (IR) injury (IRI) is associated with poor prognoses in the settings of both cardiac surgery and ischemic heart disease and causes mitochondrial oxidative stress and cell death. Silent information regulator 1 (SIRT1), a member of the histone deacetylase family, exerts anti-IRI effects. Bakuchiol (BAK), an analog of resveratrol and a monoterpene phenol isolated from the seeds of Psoralea corylifolia (Leguminosae), protects tissues from injury. This study was designed to investigate the protective effects of BAK treatment in the setting of myocardial IRI and to elucidate the potential mechanism of those effects. Prior to induction of IR, isolated rat hearts or cardiomyocytes were exposed to BAK in either the absence or presence of the SIRT1 inhibitors Sirtinol and SIRT1 siRNA. BAK exerted cardioprotective effects, as evidenced by the improvements noted in cardiac function following ischemia, attenuated myocardial apoptosis, and changes in several biochemical parameters (including increases in the level of the anti-apoptotic protein Bcl2, decreases in the level of the pro-apoptotic protein Bax, and decreases in the cleaved Caspase 3 level). However, Sirtinol and SIRT1 siRNA each blocked BAK-induced cardioprotection by inhibiting SIRT1 signaling. Additionally, BAK significantly increased the activities of mitochondrial succinate dehydrogenase, cytochrome c oxidase, and mitochondrial superoxide dismutase and decreased the production of malondialdehyde. These findings suggested that BAK significantly attenuated IR-induced mitochondrial oxidative damage. However, Sirtinol and SIRT1 siRNA abolished BAK-dependent mitochondrial function. In summary, our results demonstrate that BAK treatment attenuates IRI by attenuating IR-induced mitochondrial oxidative damage via the activation of SIRT1/PGC-1α signaling.

PubMed Feng, Jianyu; Yang, Yang; Zhou,Yajun; Wang, Bodong; Xiong,Hongyan; Fan, Chongxi; Jiang, Shuai;Liu, Jun; Ma, Zhiqiang; Hu, Wei; Li,Tian; Feng, Xiao; Xu, Jianjun; Jin,Zhenxiao 2016-05-01 Apoptosis: an international journal on programmed cell death DOI: 10.1007/s10495-016-1225-6 ISSN: 1360-8185 Volume: 21 Issue: 5 Pages: 532-45 PMID: 27000151

Antioxidant

Psoralen and Bakuchiol Ameliorate M-CSF Plus RANKL-Induced Osteoclast Differentiation and Bone Resorption Via Inhibition of AKT and AP-1 Pathways in Vitro.

Psoralen and bakuchiol are the main active compounds found in the traditional Chinese medicine Psoralea corylifolia L. and have been used to treat osteoporosis. This study aims to investigate the anti-osteoporosis effects of these two compounds using osteoclasts precursor differentiation and bone absorption assays in vitro. Primary mouse osteoclasts precursor cells were induced by M-CSF (macrophage colony stimulating factor) plus RANKL (receptor activator of nuclear factor kappa-B ligand) in vitro. TRACP (tartrate-resistant acid phosphatase) enzyme activity and toluidine blue staining were used to observe the effects of psoralen and bakuchiol on osteoclast differentiation and bone resorption, respectively. Gelatin zymography was used to assess MMP (matrix metalloproteinase) activity, and ELISA was performed to measure cathepsin K activity. Western blotting analysis for expression of phosphorylated AKT, ERK, NF-kB, and c-jun; and immunofluorescence analysis for c-jun and p65 nuclear translocation in induced osteoclasts were then used to determine the mechanism of anti-bone resorption of psoralen and bakuchiol. Mature osteoclasts were induced by M-CSF plus RANKL from primary bone marrow macrophages in vitro. Both psoralen and bakuchiol significantly inhibited TRACP enzyme activity and slightly decreased the number of TRACP+ multinuclear osteoclasts induced by M-CSF plus RANKL. Bakuchiol significantly decreased bone lacunae area and attenuated MMP-2 activity induced by M-CSF plus RANKL in osteoclasts. Both psoralen and bakuchiol significantly decreased the expression and nuclear translocation of phosphorylated c-jun stimulated by M-CSF plus RANKL, but no significant effect on p65 translocation was observed in osteoclasts. Additionally, bakuchiol significantly attenuated the increased of M-CSF plus RANKL-induced phosphorylation of AKT in osteoclasts. Psoralen and bakuchiol ameliorated M-CSF plus RANKL-induced osteoclast differentiation and bone resorption via inhibition of AKT and AP-1 pathways activation in vitro.

PubMed Chai, Lijuan; Zhou, Kun; Wang, Shaoxia; Zhang, Han; Fan, Na; Li, Jie; Tan, Xiaofeng; Hu, Limin; Fan, Xiang 2018-01-01 Cellular physiology and biochemistry: international journal of experimental cellular physiology,biochemistry, and pharmacology DOI: 10.1159/000492554 ISSN: 1015-8987 Volume: 48 Issue: 5 Pages:2123-2133 PMID: 30110702

Antioxidant

Inhibition of mitochondrial lipid peroxidation by Bakuchiol, a meroterpene from Psoralea corylifolia.

Bakuchiol, a meroterpene isolated from Psoralea corylifolia, prevented mitochondrial lipid peroxidation. Inhibition of oxygen consumption originating in lipid peroxidation was time-dependent. Bakuchiol protected mitochondrial respiratory enzyme activities against both NADPH-dependent and dihydroxyfumarate-induced peroxidation injury. Bakuchiol was shown to be effective to protect mitochondrial functions against oxidative stress.

PubMed Haraguchi, H; Inoue, J; Tamura, Y;Mizutani, K2000-08-01 Planta medica

Antioxidant

Hypoxia-inducible factor-1 and nuclear factor-kappaB inhibitory meroterpene analogues of bakuchiol, a constituent of the seeds of Psoralea corylifolia.

Two new meroterpenoids, 12,13-dihydro-12,13-dihydroxybakuchiol (2) and (12'S)-bisbakuchiol C (3), were isolated from the seeds of Psoralea corylifolia L. (Fabaceae). The structures of 2 and 3 were elucidated by spectroscopic and chemical methods. Six meroterpenoids isolated from P. corylifolia and three semi-synthetic analogues were evaluated for HIF-1 and NF-kappaB inhibition, and O-methyl and O-ethylbakuchiols (6 and 7) inhibited HIF-1 and NF-kappaB activation without significantly decreasing the viability of the AGS and HeLa cells, respectively

PubMed Wu, Cheng-Zhu; Hong, Seong Su; Cai,Xing Fu; Dat, Nguyen Tien; Nan, Ji-Xing; Hwang, Bang Yeon; Lee, Jung Joon; Lee, Dongho 2008-04-15 Bioorganic & medicinal chemistry letters DOI: 10.1016/j.bmcl.2008.03.028 ISSN: 0960-894X Volume: 18 Issue: 8 Pages: 2619-23 PMID: 18359631

Antioxidant

Protective effects of the compounds isolated from the seed of Psoralea corylifolia on oxidative stress-induced retinal damage.

The mechanism underlying glaucoma remains controversial, but apoptosis caused by increased levels of reactive oxygen species (ROS) is thought to play a role in its pathogenesis. We investigated the effects of compounds isolated from Psoralea corylifolia on oxidative stress-induced cell death in vitro and in vivo. Transformed retinal ganglion cells (RGC-5) were treated with l-buthione-(S,R)-sulfoximine (BSO) and glutamate in the presence or with pre-treatment with compound 6, bakuchiol isolated from P. corylifolia. We observed reduced cell death in cells pre-treated with bakuchiol. Moreover, bakuchiol inhibited the oxidative stress-induced decrease of mitochondrial membrane potential (MMP, ΔΨm). Furthermore, while intracellular Ca(2+) was high in RGC-5 cells after exposure to oxidative stress, bakuchiol reduced these levels. In an in vivo study, in which rat retinal damage was induced by intravitreal injection of N-methyl-d-aspartate (NMDA), bakuchiol markedly reduced translocation of AIF and release of cytochrome c, and inhibited up-regulation of cleaved caspase-3, cleaved caspase-9, and cleaved PARP. The survival rate of retinal ganglion cells (RGCs) 7days after optic nerve crush (ONC) in mice was significantly decreased; however, bakuchiol attenuated the loss of RGCs. Moreover, bakuchiol attenuated ONC-induced up-regulation of apoptotic proteins, including cleaved PARP, cleaved caspase-3, and cleaved caspase-9. Bakuchiol also significantly inhibited translocation of mitochondrial AIF into the nuclear fraction and release of mitochondrial cytochrome c into the cytosol. These results demonstrate that bakuchiol isolated from P. corylifolia has protective effects against oxidative stress-induced retinal damage and may be considered as an agent for treating or preventing retinal degeneration.

PubMed Kim, Kyung-A; Shim, Sang Hee; Ahn, Hong Ryul; Jung, Sang Hoon 2013-06-01 Toxicology and applied pharmacology DOI: 10.1016/j.taap.2013.03.017 ISSN: 0041-008X Volume: 269 Issue:2 Pages: 109-20 PMID: 23545180

Antimicrobial

Antiphytopathogenic activity of Psoralea glandulosa (Fabaceae) against Botrytis cinerea and Phytophthora cinnamomi.

The resinous exudate, three meroterpenes, namely bakuchiol (1), 3-hydroxybakuchiol (2), 12-hydroxyisobakuchiol (3), and one furanocoumarin, psoralen (4), were isolated from the leaves of culen (Psoralea glandulosa). In addition to these, two semi-synthetic derivatives, bakuchiol acetate (5) and bakuchiol methyl eter (6), were obtained from 1, and were subsequently evaluated in vitro for the inhibitory effect of resin and compounds on the mycelial growth of Botrytis cinerea Pers.: Fr. and Phytophthora cinnamomi Rands. The resinous exudate inhibited the mycelial growth of both the pathogens, while bakuchiol (1) exhibited an inhibitory effect on the mycelial growth of B. cinerea up to 94% at a concentration of 150 mg/L and psoralen (4) reduced the mycelial growth of P. cinnamomi up to 80% at a concentration of 150 mg/L. These compounds have the ability of blocking the development of mycelial growth and may be used as a potential biopesticide in the agricultural sector once the in vivo test results have been validated

PubMed Madrid Villegas, Alejandro; Díaz Peralta, Katy; González Tapia, César; Catalán Marín, Karen; Espinoza Catalán, Luis 2015-01-01 Natural product research DOI:10.1080/14786419.2014.955486 ISSN: 1478-6419 Volume: 29 Issue: 6 Pages: 586-8 PMID: 25184663

Antimicrobial

Characteristics of bakuchiol - the compound with high biological activity and the main source of its acquisition - Cullen corylifolium (L.) Medik.

The article presents the characteristics of bakuchiol - a natural compound valuable in cosmetology and pharmacology. The only source for obtaining this specific meroterpenic phenol is the fruit of the species Cullen corylifolium ( Psoralea corylifolia ). Bakuchiol has recently been playing a significant role in cosmetology as a "natural substitute" for retinol, free of side effects. Clinical studies confirm valuable cosmetological properties of bakuchiol, such as anti-ageing, anti-pigmentation and anti-acne effects. Scientific research has also shown valuable pharmacological properties of bakuchiol, such as anti-cancer, hepatoprotective, cardioprotective, hypoglycemic, hypolipemic, and antidepressant. In addition, antioxidant, anti-inflammatory and antimicrobal activities of bakuchiol, valuable from the point of view of both cosmetology and therapy, have also been confirmed. A separate part of the article is devoted to the botanical, chemical and pharmacological characteristics of the species C. corylifolium as the main source for obtaining bakuchiol

PubMed Jafernik, Karolina; Halina, Ekiert;Ercisli, Sezai; Szopa, Agnieszka 2020-11-13 Natural product research DOI:10.1080/14786419.2020.1837813 ISSN: 1478-6419 Pages: 1-15 PMID:33185126

Antimicrobial

Bakuchiol Is a Phenolic Isoprenoid with Novel Enantiomer-selective Anti-influenza A Virus Activity Involving Nrf2 Activation*

Influenza represents a substantial threat to human health and requires novel therapeutic approaches. Bakuchiol is a phenolic isoprenoid compound present in Babchi (Psoralea corylifolia L.) seeds. We examined the anti-influenza viral activity of synthetic bakuchiol using Madin-Darby canine kidney cells. We found that the naturally occurring form, (+)-(S)-bakuchiol, and its enantiomer, (−)-(R)-bakuchiol, inhibited influenza A viral infection and growth and reduced the expression of viral mRNAs and proteins in these cells. Furthermore, these compounds markedly reduced the mRNA expression of the host cell influenza A virus-induced immune response genes, interferon-β and myxovirus-resistant protein 1. Interestingly, (+)-(S)-bakuchiol had greater efficacy than (−)-(R)-bakuchiol, indicating that chirality influenced anti-influenza virus activity. In vitro studies indicated that bakuchiol did not strongly inhibit the activities of influenza surface proteins or the M2 ion channel, expressed in Chinese hamster ovary cells. Analysis of luciferase reporter assay data unexpectedly indicated that bakuchiol may induce some host cell factor(s) that inhibited firefly and Renilla luciferases. Next generation sequencing and KeyMolnet analysis of influenza A virus-infected and non-infected cells exposed to bakuchiol revealed activation of transcriptional regulation by nuclear factor erythroid 2-related factor (Nrf), and an Nrf2 reporter assay showed that (+)-(S)-bakuchiol activated Nrf2. Additionally, (+)-(S)-bakuchiol up-regulated the mRNA levels of two Nrf2-induced genes, NAD(P)H quinone oxidoreductase 1 and glutathione S-transferase A3. These findings demonstrated that bakuchiol had enantiomer-selective anti-influenza viral activity involving a novel effect on the host cell oxidative stress response.

PubMed Central Shoji, Masaki; Arakaki, Yumie; Esumi,Tomoyuki; Kohnomi, Shuntaro;Yamamoto, Chihiro; Suzuki, Yutaka;Takahashi, Etsuhisa; Konishi, Shiro;Kido, Hiroshi; Kuzuhara, Takashi 2015-10-07 The Journal of Biological Chemistry DOI: 10.1074/jbc.M115.669465 ISSN:0021-9258 Volume: 290 Issue: 46 Pages: 28001-28017 PMID:26446794

Antimicrobial

In Vitro Antimicrobial Activities of Bakuchiol against Oral Microorganisms

Bakuchiol was isolated from the seeds of Psoralea corylifolia, a tree native to China with various uses in traditional medicine, followed by extraction with ether and column chromatography combined with silica gel and octyldecyl silane. In this study, the antimicrobial activities of bakuchiol against some oral microorganisms were evaluated in vitro. The cell growth of Streptococcus mutans was inhibited in a bakuchiol concentration-dependent manner, and growth of S. mutans was completely prevented by 20 μg of bakuchiol per ml. The bactericidal effect of bakuchiol on S. mutans was dependent on temperature and stable under the following conditions: sucrose, 0 to 10% (wt/vol); pH, 3.0 to 7.0; organic acids (3% [wt/vol] citric and malic acids). Bakuchiol showed bactericidal effects against all bacteria tested, including S. mutans, Streptococcus sanguis, Streptococcus salivarius, Streptococcus sobrinus, Enterococcus faecalis, Enterococcus faecium, Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus plantarum, Actinomyces viscosus, and Porphyromonas gingivalis, with MICs ranging from 1 to 4 μg/ml and the sterilizing concentration for 15 min ranging from 5 to 20 μg/ml. Furthermore, bakuchiol was also effective against adherent cells of S. mutans in water-insoluble glucan in the presence of sucrose and inhibited the reduction of pH in the broth. Thus, bakuchiol would be a useful compound for development of antibacterial agents against oral pathogens and has great potential for use in food additives and mouthwash for preventing and treating dental caries.

PubMed Central Katsura, Harumi; Tsukiyama, Ryo-Ichi; Suzuki, Akiko; Kobayashi, Makio 2001-11 Antimicrobial Agents and Chemotherapy DOI: 10.1128/AAC.45.11.3009-3013.2001 ISSN: 0066-4804 Volume:45 Issue: 11 Pages: 3009-3013 PMID:11600349

Ant inflammatory

Quantitative Analysis of Psoralea corylifolia Linne and its Neuroprotective and Anti-Neuroinflammatory Effects in HT22 Hippocampal Cells and BV-2 Microglia

The seeds of Psoralea corylifolia L. (P. corylifolia), also known as “Bo-Gol-Zhee” in Korea, are used in a traditional herbal medicine for treating various skin diseases. In the present study, we performed quantitative analyses of the seven standard components of P. corylifolia: psoralen, angelicin, neobavaisoflavone, psoralidin, isobavachalcone, bavachinin, and bakuchiol, using high-performance liquid chromatography. We also investigated the neuroprotective and anti-neuroinflammation effects of P. corylifolia and its standard components in the hippocampal cell line HT22 and microglia cell line BV-2. A 70% ethanol extract of P. corylifolia was prepared and the seven standard components were separated using C-18 analytical columns by gradient solvents with acetonitrile and water, and ultraviolet detection at 215, 225 and 275 nm. The analytical method showed high linearity, with a correlation coefficient of ≥0.9999. The amounts of the standard components ranged from 0.74 to 11.71 mg/g. Among the components, bakuchiol (11.71 mg/g) was the most potent phytochemical component of P. corylifolia. Furthermore, we analyzed the inhibitory effects of the components from P. corylifolia to determine the bioactive compound needed to regulate neuronal cell changes. Angelicin, isobavachalcone, and bakuchiol suppressed lipopolysaccharide (LPS)-stimulated nitric oxide production in LPS-treated BV-2 microglia more significantly than did the other components. In HT22 hippocampal cells, neobavaisoflavone and bakuchiol had more potent inhibitory activity against hydrogen peroxide-induced cell death. Taken together of the quantification and efficacy analyses, bakuchiol appeared to be the most potent bioactive phytochemical component of P. corylifolia for the potential treatment of neurodegenerative diseases

PubMed Central Kim, Yu Jin; Lim, Hye-Sun; Lee, Jun;Jeong, Soo-Jin 2016-08-17 Molecules DOI: 10.3390/molecules21081076 ISSN: 1420-3049 Volume: 21 Issue: 8 PMID: 27548120

Anti-inflammatory

Evaluation of the immunomodulatory and anti-inflammatory activity of Bakuchiol using RAW 264.7 macrophage cell lines and in animal models stimulated by lipopolysaccharide (LPS).

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).

PubMed Kumar, Amit; Sawhney, Gifty; Kumar Nagar, Rakesh; Chauhan, Narendra;Gupta, Nidhi; Kaul, Anpurna; Ahmed, Zabeer; Sangwan, P L; Satheesh Kumar, P; Yadav, Govind 2021-02-01 International immunopharmacology DOI: 10.1016/j.intimp.2020.107264 ISSN: 1567-5769 Volume: 91 Pages: 107264 PMID: 33340782

Anti-inflammatory

Isolation and anti-inflammatory activity of Bakuchiol from Ulmus davidiana var. japonica.

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.

ubMed Choi, Sang Yoon; Lee, Sanghyun;Choi, Won-Hee; Lee, Yeonmi; Jo,Youn Ock; Ha, Tae-Youl 2010-08-01 Journal of medicinal food DOI: 10.1089/jmf.2009.1207 ISSN: 1096-620X Volume: 13 Issue: 4 Pages: 1019-23 PMID: 20553183

Anticancer

Psoralea glandulosa as a Potential Source of Anticancer Agents for Melanoma Treatment

With the aim of identifying novel agents with antigrowth and pro-apoptotic activity on melanoma cancer, the present study was undertaken to investigate the biological activity of the resinous exudate of aerial parts from Psoralea glandulosa, and its active components (bakuchiol (1), 3-hydroxy-bakuchiol (2) and 12-hydroxy-iso-bakuchiol (3)) against melanoma cells (A2058). In addition, the effect in cancer cells of bakuchiol acetate (4), a semi-synthetic derivative of bakuchiol, was examined. The results obtained show that the resinous exudate inhibited the growth of cancer cells with IC50 value of 10.5 μg/mL after 48 h of treatment, while, for pure compounds, the most active was the semi-synthetic compound 4. Our data also demonstrate that resin is able to induce apoptotic cell death, which could be related to an overall action of the meroterpenes present. In addition, our data seem to indicate that the apoptosis correlated to the tested products appears, at least in part, to be associated with an increase of reactive oxygen species (ROS) production. In summary, our study provides the first evidence that P. glandulosa may be considered a source of useful molecules in the development of analogues with more potent efficacy against melanoma cells.

PubMed Central Madrid, Alejandro; Cardile, Venera;González, César; Montenegro, Ivan;Villena, Joan; Caggia, Silvia; Graziano,Adriana; Russo, Alessandra 2015-04-09 International Journal of Molecular Sciences DOI: 10.3390/ijms16047944 ISSN: 1422-0067 Volume: 16 Issue: 4 Pages: 7944-7959 PMID: 25860949

Anticancer

Vitro antitumor activity and synthesis of the key intermediate of bakuchiol

The in vitro antitumor activity of bakuchiol was exploited, compared with tamoxifen. The result of biological activities showed that bakuchiol could inhibit human breast cancer and the IC50 values were 2.89 x 10(-5) mol L(-1) and 8.29 x 10(-3) mol L(-1) against the cells line T-47D and MDA-MB-231 respectively. On the other hand, the key intermediate to synthesize bakuchiol was obtained by the method of Ireland-Claisen rearrangement. Comparing with traditional Claisen rearrangement, the reaction conditions are milder and the reaction reagents are safer

PubMed Chen, Hong-li; Feng, Hui-jin; Li, Yuan-chao 2010-04-01 Yao xue xue bao = Acta pharmaceutica Sinica ISSN: 0513-4870 Volume: 45 Issue: 4 Pages: 467-70 PMID: 21355211

Anticancer

Effect of bakuchiol on leukocyte functions and some inflammatory responses in mice.

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

PubMed Ferrándiz, M L; Gil, B; Sanz, M J; Ubeda, A; Erazo, S; González, E; Negrete, R; Pacheco, S; Payá, M;Alcaraz, M J 1996-09-01 The Journal of pharmacy and pharmacology DOI: 10.1111/j.2042-7158.1996.tb06016.x ISSN: 0022-3573 Volume: 48 Issue: 9 Pages: 975-80 PMID: 8910867

Anticancer

In vivo pharmacokinetics of bakuchiol after oral administration of bakuchiol extraction in rat plasma.

Psoralea corylifolia L. (Fabaceae) was a traditional Chinese medicine for the treatment of various skin diseases such as psoriasis, vitiligo and chronic graft-versus-host, and has been proved to show anticancer, cytotoxic, anti-bacterial, cardiac, diaphoretic, diuretic, stimulant, aphrodisiac and tonic effects. Bakuchiol was one of the main active ingredients of this traditional Chinese medicine. In this paper, pharmacokinetic study was conducted to obtain pharmacokinetic parameters of bakuchiol. Bakuchiol was enriched using resin inform the ethanol extract of Psoralea corylifolia L., HPLC-UV was used to determine the concentration of bakuchiol in rat plasma at different time points after administration. The main pharmacokinetic parameters of bakuchiol in rat were obtained based on the analysis of the plasma sample. The pharmacokinetics of bakuchiol was fitted with a two-compartment model and it was eliminated relative slowly in rats. The HPLC-UV method was successfully applied to study the pharmacokinetics of bakuchiol in rats

PubMed Yan, Dong-Mei; Chang, Yan-Xu; Wang, Yue-Fei; Liu, Er-Wei; Li, Jin; Kang, Li-Yuan; Gao, Xiu-Mei 2010-04-21 Journal of ethnopharmacology DOI: 10.1016/j.jep.2009.12.039 ISSN: 0378-8741 Volume: 128 Issue: 3 Pages: 697-702 PMID: 20051255

Anticancer

Preparation and in vitro evaluation of radioiodinated bakuchiol as an anti tumor agent.

Bakuchiol, extracted from the plant Psoralea corylifolia, has been proven to have anti-tumor, cytotoxic, anti-microbial and anti-inflammatory activity. In order to study if radiolabeled bakuchiol exhibits enhanced cytotoxicity, bakuchiol was radiolabeled with 125I. In-vitro uptake studies of 125I-bakuchiol were carried out using LS-A (lymphosarcoma) and barcl-95 (radiation-induced thymic lymphoma) ascitic and solid tumor cells of murine origin. In both LS-A and barcl-95, 125I-bakuchiol showed significant uptake. Viability studies showed that the radioiodinated compound showed greater cytotoxic effect than bakuchiol

PubMed Bapat, Ketaki; Chintalwar, G J;Pandey, Usha; Thakur, V S; Sarma, HD; Samuel, Grace; Pillai, M R A; Chattopadhyay, S; Venkatesh, Meera 2005-03-01 Applied radiation and isotopes : including data, instrumentation and methods for use in agriculture, industry and medicine

Anticancer

Bakuchiol suppresses proliferation of skin cancer cells by directly targeting Hck, Blk, and p38 MAP kinase

Bakuchiol is a meroterpene present in the medicinal plant Psoralea corylifolia, which has been traditionally used in China, India, Japan and Korea for the treatment of premature ejaculation, knee pain, alopecia spermatorrhea, enuresis, backache, pollakiuria, vitiligo, callus, and psoriasis. Here, we report the chemo preventive properties of bakuchiol, which acts by inhibiting epidermal growth factor (EGF)-induced neoplastic cell transformation. Bakuchiol also decreased viability and inhibited anchorage-independent growth of A431 human epithelial carcinoma cells. Bakuchiol reduced A431 xenograft tumor growth in an in vivo mouse model. Using kinase profiling, we identified Hck, Blk and p38 mitogen activated protein kinase (MAPK) as targets of bakuchiol, which directly bound to each kinase in an ATP-competitive manner. Bakuchiol also inhibited EGF-induced signaling pathways downstream of Hck, Blk and p38 MAPK, including the MEK/ERKs, p38 MAPK/MSK1 and AKT/p70S6K pathways. This report is the first mechanistic study identifying molecular targets for the anticancer activity of bakuchiol and our findings indicate that bakuchiol exhibits potent anticancer activity by targeting Hck, Blk and p38 MAPK.

National Library of Medicine's (NLM)PubMed Central (PMC)Lee, Younghyun; Yang, Hee; Heo,Yong-Seok; Bode, Ann M.; Lee, KiWon; Dong, Zigang 2016-02-20 Oncotarget DOI: 10.18632/oncotarget.7524 ISSN: 1949-2553 Volume: 7 Issue: 12 Pages: 14616-14627 PMID:26910280

Anticancer

Bakuchiol inhibits cell proliferation and induces apoptosis and cell cycle arrest in SGC-7901 human gastric cancer cells.

The main purpose of the present study was to evaluate the antiproliferative activity of bakuchiol in human gastric tumor cell line (SGC-7901) along with an effort to demonstrate its mode of action. he effect of the compound on cell viability was evaluated by MTT assay. Fluorescence and phase contrast microscopic techniques were used to study the effect of the compound on cellular morphology and apoptosis. Flow cytometry was used to assess the effect on cell cycle phase distribution. The results revealed that bakuchiol exerted potent, dose-dependent as well as time-dependent growth inhibitory effects in SGC-7901 cell proliferation with IC50 values of 58.4, 42.3 and 32.5 μM at 12, 24 and 48 hrs time intervals, respectively. On treatment with 10, 50 and 100 μM dose of bakuchiol for 48 hrs, phase contrast microscope revealed that the cells got detached from one another making clusters of small number of cells floating in the medium. After the cells were treated with 10, 50 and 100 μM of bakuchiol, cells began to emit orange red fluorescence more heavily at the centre of cells indicating apoptosis. Bakuchiol also induced sub-G1 cell cycle arrest in a dose-dependent manner. The current findings reveal that bakuchiol is a potent cytotoxic agent against gastric cancer cells and its cytotoxicity is mediated through induction of apoptosis and sub-G1 cell cycle arrest

PubMed Lin, Jing; Yao, Hui-Jing; Li, Rui-Yun 2016-01-01 Journal of B.U.ON. :official journal of the Balkan Union of Oncology ISSN: 1107-0625 Volume: 21 Issue: 4 Pages: 889-894 PMID: 27685910

Anticancer

Phytoestrogen Bakuchiol Exhibits In Vitro and In Vivo Anti-breast Cancer Effects by Inducing S Phase Arrest and Apoptosis

Phytoestrogen has been proposed as an alternative to hormone replacement therapy, which has been demonstrated to promote a high risk of breast cancer. However, the effect of phytoestrogen on breast cancer development has not been fully understood. Bakuchiol is an active ingredient of a traditional Chinese herbal medicine Fructus Psoraleae, the dried ripe fruit of Psoralea corylifolia L. (Fabaceae). The in vitro and in vivo estrogenic activities and anti-breast cancer effects of bakuchiol have not been well-studied. We found that bakuchiol induced the GFP expression in transgenic medaka (Oryzias melastigma, Tg, Chg:GFP) dose-dependently (0–1 μg/ml), demonstrating its in vivo estrogenic activity. Low dose of bakuchiol (1 μg/ml) induced the cell proliferation and ERα expression in MCF-7 cells, which could be blocked by the anti-estrogen ICI 182780, suggesting the in vitro estrogenic activity of bakuchiol. Our data indicated that high doses of bakuchiol (>2 μg/ml) inhibited breast cancer cell growth, with a stronger anti-proliferative effect than resveratrol, a widely studied analog of bakuchiol. High doses of bakuchiol (4, 7, and 10 μg/ml) were used for the further in vitro anti-breast cancer studies. Bakuchiol induced ERβ expression and suppressed ERα expression in MCF-7 cells. It also induced S phase arrest in both MCF-7 and MDA-MB-231 cells, which could be rescued by caffeine. Knock-down of p21 also marginally rescued S phase arrest in MCF-7 cells. The S phase arrest was accompanied by the upregulation of ATM, P-Cdc2 (Tyr15), Myt1, P-Wee1 (Ser642), p21 and Cyclin B1, suggesting that blocking of Cdc2 activation may play an important role in bakuchiol-induced S phase arrest. Furthermore, bakuchiol induced cell apoptosis and disturbed mitochondrial membrane potential in MCF-7 cells. The bakuchiol-induced apoptosis was associated with increased expression of Caspase family and Bcl-2 family proteins, suggesting that bakuchiol may induce apoptosis via intrinsic apoptotic pathway. The in vivo anti-breast cancer effect of bakuchiol was further proved in zebrafish (Danio rerio, wild-type AB) xenografts. 0.5 μg/ml of bakuchiol significantly reduced the MCF-7 cell mass in zebrafish xenografts. Overall, these results suggested the potential of using bakuchiol in HRT and breast cancer treatment.

PubMed Central Li, Li; Chen, Xueping; Liu, Chi C.; Lee,Lai S.; Man, Cornelia; Cheng, Shuk H.2016-05-24 Frontiers in Pharmacology DOI: 10.3389/fphar.2016.00128 ISSN: 1663-9812 Volume: 7 PMID:27252650

Anticancer

Bakuchiol sensitizes cancer cells to TRAIL through ROS- and JNK-mediated upregulation of death receptors and downregulation of survival proteins.

We investigated whether bakuchiol, an analog of resveratrol enhances the apoptosis ability of tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) in cancer cells. Bakuchiol enhanced expression of cell death receptor (DR) in TRAIL-sensitive and -resistant colon cancer cells in a dose-dependent manner. A combination of bakuchiol with TRAIL significantly inhibited cell growth of TRAIL sensitive HCT116 and TRAIL resistant HT-29 cells. The expression of TRAIL receptors; DR4 and DR5 was significantly increased by treatment of bakuchiol, however, the expression of survival proteins (e.g., cFLIP, survivin, XIAP and Bcl2) was suppressed. Moreover, the expression of apoptosis related proteins such as cleaved caspase-3, -8, -9 and PARP was increased by combination treatment of bakuchiol and TRAIL. Depletion of DR4 or DR5 by small interfering RNA significantly reversed the cell growth inhibitory effects of bakuchiol in HCT116 and HT-29 cells. Pretreatment with the c-Jun N-terminal kinase (JNK) inhibitor SP600125 and the reactive oxygen species (ROS) scavenger N-acetylcysteine reduced the bakuchiol induced cell growth inhibitory effects. The collective results suggest that bakuchiol facilitates TRAIL-induced apoptosis in colon cancer cells through up-regulation of the TRAIL receptors; DR4 and DR5 via ROS/JNK pathway signals

PubMed Park, Mi Hee; Kim, Jong Han; Chung,Young-Ho; Lee, Seung Ho 2016-04-29 Biochemical and biophysical research communications DOI: 10.1016/j.bbrc.2016.03.127 ISSN: 0006-291X Volume: 473 Issue:2 Pages: 586-92 PMID: 27033605

Anticancer

Bakuchiol exhibits anti-metastasis activity through NF-κB cross-talk signaling with AR and ERβ in androgen-independent prostate cancer cells PC-3.

Androgen-independent prostate cancer (PCa) is a developed tumor derived from the local androgen dependent PCa, which often affects elderly men. Psoralea corylifolia L, a traditional Chinese medicine, has been widely used for PCa treatment as an important part of a common prescription, while the mechanism remains unclear. Our study was aimed to investigate the tumor-inhibitory effect of its main component bakuchiol in androgen-independent PCa cell line PC-3 cells. Bakuchiol significantly suppressed PC-3 cell proliferation and migration; the expressions of PCNA and MMP-9 were consistently down regulated as well. Meanwhile, both the constitutive and LPS-induced NF-κB activation were significantly inhibited by bakuchiol. The inhibitory effects of bakuchiol on cell proliferation, migration and invasion were recovered when LPS were added together with bakuchiol. SiRNA against androgen receptor (AR) or estrogen receptor β (ERβ) were transfected and the regulation of bakuchiol-suppressed proliferation, invasion, NF-κB signaling and MMP-9 secretion in response to LPS were blocked. Taken together, our data demonstrated that bakuchiol inactivated NF-κB signaling via AR and ERβ, which contributes to inhibition of PC-3 cell proliferation and migration, indicating that bakuchiol is one of the key component from P. corylifolia L for PCa treatment and has a potential as anti-prostate cancer drug candidates

PubMed Miao, Lin; Yun, Xiaoting; Tao, Rui; Wang, Yuefei; Fan, Guanwei; Zhu, Yan; Cai, Ting; Zhu, Zhipeng; Yan, Chunlin; Gao, Xiumei 2018-09-01 Journal of pharmacological sciences DOI: 10.1016/j.jphs.2017.04.004 ISSN: 1347-8613 Volume: 138 Issue: 1 Pages: 1-8 PMID: 30236540

Oestrogenic activity

Positive skeletal effect of two ingredients of Psoralea corylifolia L. on estrogen deficiency-induced osteoporosis and the possible mechanisms of action.

Estrogen replacement therapy (ERT) is utilized as a major regime for treatment of postmenopausal osteoporosis at present. However, long-term supplement of estrogen may cause uterine hyperplasia and hypertension leading to a high risk of endometrial cancer and breast cancer. Psoralea corylifolia L. has long been used as tonic and food additives in many countries. Previous studies had found two ingredients in P. corylifolia L.: bavachin and bakuchiol exhibited osteoblastic activity. The present study was designed to investigate the protective effect of bakuchiol and bavachin on ovariectomy-induced bone loss and explore the possible mechanism. In vivo, bakuchiol and bavachin could prevented estrogen deficiency-induced bone loss in ovariectomized rats without uterotrophic activity. In vitro studies suggested that bakuchiol and bavachin induced primary human osteoblast differentiation by up-regulating the Wnt signalling pathway. This study suggests that such a bone-protective role makes them a promising and safe estrogen supplement for the ERT.

PubMed Weng, Ze-Bin; Gao, Qian-Qian; Wang, Fang; Zhao, Gen-Hua; Yin, Fang-Zhou; Cai, Bao-Chang; Chen, Zhi-Peng; Li, Wei-Dong 2015-12-05 Molecular and cellular endocrinology DOI: 10.1016/j.mce.2015.09.025 ISSN: 0303-7207 Volume: 417 Pages: 103-13 PMID: 26419930

Oestrogenic activity

Ethanol extract of Psoralea corylifolia L. and its main constituent, bakuchiol, reduce bone loss in ovariectomised Sprague-Dawley rats.

The aim of the present study was to investigate whether ethanol extracts of Psoralea corylifolia L. (PCE) and its active component protect against bone loss in ovariectomised rats. We screened oestrogenic activities of the main extract fractions using in vitro assays and identified bakuchiol as the most active oestrogenic component by HPLC and LC/MS, and then demonstrated that bakuchiol had strong binding affinity for oestrogen receptor (ER) alpha. Seventy female Sprague-Dawley rats were assigned to either a sham-operated group (n 10) or an ovariectomised group (n 60). The ovariectomised group was subdivided into six groups, each containing ten rats: vehicle group, two bakuchiol-treated groups (dose of 15 mg/kg per d or 30 mg/kg per d; ten rats for each group), two PCE-supplemented groups (0.25 % or 0.5 % extracts of diets; ten rats for each group) and a 17beta-oestradiol (E2)-treated group (20 microg/kg per d). We recorded weight and feed intake every week, and killed all animals after 6 weeks. Blood was collected, and the uterus, kidneys and livers were removed. Bakuchiol has a three-fold higher binding affinity for ERalpha than for ERbeta. Bakuchiol and PCE treatments had no uterotrophic activity even though they demonstrated oestrogenic activity in the in vitro assays. Bakuchiol and PCE treatments reduced postmenopausal bone loss by increasing alkaline phosphatase, Ca concentrations, serum E2 concentration and bone mineral density, and by decreasing the inorganic P level. The present study indicated that bakuchiol and PCE treatments could protect against bone loss.

PubMed Lim, Sun-Hye; Ha, Tae-Youl; Kim, Sung-Ran; Ahn, Jiyun; Park, Hyun Jin; Kim, Suna 2009-04-01 The British journal of nutrition DOI: 10.1017/S0007114508066750 ISSN: 0007-1145 Volume: 101 Issue: 7 Pages: 1031-9 PMID: 18801207

Cytotoxic Agent

Bakuchiol derivatives as novel and potent cytotoxic agents: a report.

A library of 28 compounds comprising of acyl, amino, halo, nitro, styryl and cyclized derivatives of bakuchiol have been evaluated against a panel of eight human cancer cell lines. Bioevaluation studies have resulted in the identification of potent cytotoxic molecules exhibiting concentration dependent growth inhibition against leukemia cancer cells with best results observed for compounds 17 and 22 exhibiting IC(50) 1.8 and 2.0 μM respectively. As evident from various biological end-points, inhibition of cell proliferation by inducing G2/M cell cycle arrest, mitochondrial membrane disruption followed by DNA fragmentation and apoptosis is demonstrated

PubMed Majeed, Rabiya; Reddy, Mallepally V; Chinthakindi, Praveen K; Sangwan, Payare L; Hamid, Abid; Chashoo, Gousia; Saxena, Ajit K; Koul, Surrinder 2012-03-01 European journal of medicinal chemistry DOI: 10.1016/j.ejmech.2011.12.018 ISSN: 0223-5234 Volume: 49 Pages: 55-67 PMID: 22245048