SANTA CLARA, CA, United States
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Zhao H.,Sunny Biodiscovery, Inc. | Deneau J.,Sunny Biodiscovery, Inc. | Che G.O.L.,Institute of Chinese Medical science | Li S.,Institute of Chinese Medical science | And 6 more authors.
European Journal of Dermatology | Year: 2012

This report characterizes an aqueous isolate (SBD.4) of one of the most broadly used Chinese medicinal herbs, Angelica sinensis, from the perspective of its application in skin and wound care. SBD.4 has been chemically defined and was found to increase the strength of healed wounds in retired breeder (older) rats. Furthermore, the mechanism of action of this Angelica sinensis isolate was tested in the zebrafish angiogenesis model, and in human skin substitutes by DNA microarray, revealing a bioactivity profile consistent with skin repair and regeneration. When combined with several types of wound dressings, SBD.4 increased type I collagen production in human dermal fibroblasts, and when formulated in nanosilver hydrocolloid dressing, it was found effective in chronic ulcer management in humans, demonstrating that botanical high-tech wound dressings can be successfully developed to improve the treatment of chronic lesions in humans.


PubMed | Medical University of Gdańsk, Ohio University, Sunny Biodiscovery, Inc. and Sytheon
Type: | Journal: Clinical and experimental dermatology | Year: 2017

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.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.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.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 inhibition of the signal transducer and regulator of transcription (STAT)1/3/interferon inflammatory signal transduction axis was also identified.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.


Gobis K.,Medical University of Gdańsk | Foks H.,Medical University of Gdańsk | Bojanowski K.,Sunny Biodiscovery, Inc. | Augustynowicz-Kopec E.,Institute of Tuberculosis and Pulmonary Diseases | Napiorkowska A.,Institute of Tuberculosis and Pulmonary Diseases
Bioorganic and Medicinal Chemistry | Year: 2012

A series of novel 3-cyclohexylpropanoic acid derivatives and 3-cyclohexylpropanoic acid-derived nitrogen heterocyclic compounds (1-8) have been synthesized and evaluated for tuberculostatic activity. Compounds 1a, 1c, 1e and 1f bearing benzimidazole or benzimidazole-like systems showed the most potent tuberculostatic activity against Mycobacterium tuberculosis strains with MIC values ranging from 1.5 to 12.5 μg/mL. More importantly 1a (6-chloro-2-(2-cyclohexylethyl)-4-nitro-1H-benzo[d]imidazole) and 1f (2-(2-cyclohexylethyl)-1H-imidazo[4,5-b]phenazine) appeared selective for M. tuberculosis as compared with eukaryotic cells (human fibroblasts), and other antimicrobial strains. These compounds may thus represent a novel, selective class of antitubercular agents. Additionally compound 1a stimulated type I collagen output by fibroblasts, in vitro. © 2011 Elsevier Ltd. All rights reserved.


Gobis K.,Medical University of Gdańsk | Foks H.,Medical University of Gdańsk | Suchan K.,Medical University of Gdańsk | Augustynowicz-Kopec E.,Institute of Tuberculosis and Pulmonary Diseases | And 2 more authors.
Bioorganic and Medicinal Chemistry | Year: 2015

A series of novel 2-(2-phenalkyl)-1H-benzo[d]imidazole derivatives and analogues (2a-3l) have been synthesized and evaluated for tuberculostatic activity. Benzimidazoles substituted at the C-2 position with phenethyl, styryl and 3,5-dichlorophenethyl moiety were obtained. Compounds 2g, 2h and 2i bearing methyl groups at the benzimidazole system and phenalkyl substituent at the C-2 position showed high tuberculostatic activity against Mycobacterium tuberculosis strains with MIC values ranging from 0.8 to 6.2 μg/mL (2.5-25 μM). More importantly, derivatives 2g (5,6-dimethyl-2-phenethyl-1H-benzo[d]imidazole) and 2i (2-(3,5-dichlorophenethyl)-5,6-dimethyl-1H-benzo[d]imidazole) appeared selective for M. tuberculosis as compared with eukaryotic cells: non-malignant (neonatal human dermal fibroblasts) and malignant (mouse melanoma B16-F10 cell line). These compounds may thus represent a novel, selective class of anti-tubercular agents. SAR studies resulted in interesting conclusions on structural factors affecting tuberculostatic activity. © 2015 Elsevier Ltd. All rights reserved.


PubMed | Medical University of Gdańsk, Institute of Tuberculosis and Pulmonary Diseases and Sunny Biodiscovery, Inc.
Type: Journal Article | Journal: Bioorganic & medicinal chemistry | Year: 2015

A series of novel 2-(2-phenalkyl)-1H-benzo[d]imidazole derivatives and analogues (2a-3l) have been synthesized and evaluated for tuberculostatic activity. Benzimidazoles substituted at the C-2 position with phenethyl, styryl and 3,5-dichlorophenethyl moiety were obtained. Compounds 2g, 2h and 2i bearing methyl groups at the benzimidazole system and phenalkyl substituent at the C-2 position showed high tuberculostatic activity against Mycobacterium tuberculosis strains with MIC values ranging from 0.8 to 6.2 g/mL (2.5-25 M). More importantly, derivatives 2g (5,6-dimethyl-2-phenethyl-1H-benzo[d]imidazole) and 2i (2-(3,5-dichlorophenethyl)-5,6-dimethyl-1H-benzo[d]imidazole) appeared selective for M. tuberculosis as compared with eukaryotic cells: non-malignant (neonatal human dermal fibroblasts) and malignant (mouse melanoma B16-F10 cell line). These compounds may thus represent a novel, selective class of anti-tubercular agents. SAR studies resulted in interesting conclusions on structural factors affecting tuberculostatic activity.


Chaudhuri R.K.,Sytheon Ltd. | Bojanowski K.,Sunny Biodiscovery, Inc.
International Journal of Cosmetic Science | Year: 2014

Synopsis Objective 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 - dependant and independent pathways. Methods Comparative gene expression profiling of both substances in the EpiDerm FT full thickness skin substitute model was undertaken. Furthermore, type I, III and IV collagen, as well as aquaporin 3 expression was analyzed by ELISA and/or histochemistry in human dermal fibroblasts and/or Epiderm FT skin substitutes. Results 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. Conclusion Based on these data, we propose that bakuchiol can function as an anti-ageing compound through retinol-like regulation of gene expression. A comparative gene expression profiling between retinol and bakuchiol revealed retinol-like functional properties of bakuchiol. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.


Bojanowski K.,Sunny Biodiscovery, Inc.
International Journal of Cosmetic Science | Year: 2013

Synopsis Objective Skin compartments traditionally targeted by cosmetic actives - epidermis and dermis - are anchored and nourished by the underlying hypodermis, which therefore should be a key target for skin-rejuvenating formulations. However, given the difficulty to reach even the superficial layers of the skin, and to its 'unglamorous' fatty composition, the regenerative potential of hypodermis remains largely untapped. Therefore, this study was to investigate the capacity of a cosmetic material to trigger a regenerative response in dermis and epidermis through a selective action on hypodermis. Furthermore, it aimed to establish the effect of such cosmetic material in transbuccal hypodermal delivery form, on the hypodermal precursor cells - the preadipocytes. Methods A combination of grape seed extract and soy phospholipids was formulated and standardized for elastase activity and free radical inhibition. This formulation was then used to contact the hypodermal layer of human skin biopsies and - under a transbuccal delivery vehicle form - the 3T3-L1 preadipocytes, and its effects were quantified using PCR arrays and histochemistry. Results Application of the standardized grape/soy material to the hypodermal layer of skin triggered modulation of gene expression in the upper layers of the skin and resulted in the clear morphological improvement at the dermal and epidermal levels. Furthermore, when this material was formulated in a mucoadhesive, intraoral film and applied on 3T3-L1 preadipocytes, the resulting modulation of gene expression in these cells was consistent with differentiation and detoxification effects. Conclusions These results suggest that transbuccal formulations of nutraceutical grade cosmetics have potential to induce signal transduction pathways in facial hypodermis, resulting in anti-aging effects throughout all skin compartments, including dermal and epidermal layers. © 2013 Society of Cosmetic Scientists and the Societe Francaise de Cosmetologie.


PubMed | Sunny Biodiscovery, Inc.
Type: Journal Article | Journal: International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition | Year: 2011

Type II diabetes is a metabolic disease mediated through multiple molecular pathways. Here, we report anti-diabetic effect of a standardized isolate from a fossil material - a mineraloid leonardite - in in vitro tests and in genetically diabetic mice. The mineraloid isolate stimulated mitochondrial metabolism in human fibroblasts and this stimulation correlated with enhanced expression of genes coding for mitochondrial proteins such as ATP synthases and ribosomal protein precursors, as measured by DNA microarrays. In the diabetic animal model, consumption of the Totala isolate resulted in decreased weight gain, blood glucose, and glycated hemoglobin. To our best knowledge, this is the first description ever of a fossil material having anti-diabetic activity in pre-clinical models.


Grant
Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 149.45K | Year: 2013

DESCRIPTION (provided by applicant): Psoriasis is a chronic skin disease affecting 2% of the world population. It is characterized by immune infiltrates in lesions and hyperkeratosis, and can be partially remediated with prescription medicines, such as topical retinoids. Despite their great potential, current topical retinoid drugs are typically used at suboptimal doses, due to their side effects. Adverse effects, which include skin irritation, photosensitivity and teratogenicity are common to all 1st and2nd generation retinoids. While the 3rd generation of retinoids appears to have a better teratogenicity safety profile, its skin-adverse effects such as erythema, scaling, dryness, pruritus, and burning are not improved, affecting 10-40% of patients. In an attempt to discover retinoid-like functional compounds with minimal adverse effects, we screened libraries of natural compounds from plants traditionally used for the treatment of skin diseases, with the emphasis on psoriasis. Our research yielded one product candidate (SBD.073) with desired similar gene expression profile to retinol in human skin substitutes (using DNA microarrays) but without any skin irritation, as determined by repeat insult patch test in humans. In further human studies, SBD.073 hasbeen found to be not only non-irritant and non-phototoxic, but, to the contrary, to protect skin from UV-induced erythema. Mechanistic studies showed that, similarly to retinol, SBD.073 induced F9 cell differentiation and normalized structure of the dermal-epidermal junction, but unlike retinol, it did not stimulate the expression of RARG1 - the receptor implicated in skin irritation. Moreover, this retinoid analogue was found to have an excellent anti oxidant and anti-inflammatory activity and no mutagenicity. Here, we propose to validate the proof of principle that SBD.073 is a unique drug-candidate for a greatly improved topical treatment of psoriasis in a comparative study with the existing topical retinoid treatments. We will use a combination of psoriasis-relevant assays, such as TNF-a and IL-17/IL-22 - stimulated organotypic skin substitutes, and animal models (orthokeratosis in mouse tail test, urticuli normalization in rhino mouse and teratogenesis in NMRI mouse) to demonstrate that SBD.073 exceedsthe therapeutic activity of current topical retinoid treatment modalities, while having second- to-none safety and tolerance profile. Taken together, this project should result in the establishment of a proof of principle that SBD.073 is the first skin-protectant retinol analogue fo a greatly improved topical therapy of psoriatic lesions. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Psoriasis is a chronic autoimmune disease affecting millions of people worldwide, in which the immune infiltrates disrupt normal keratinization of the skin. Among the available treatments, retinoids are an important therapeutic option, which is however limited by side effects (retinoid dermatitis, teratogenicity, photosensitivity), which adversely affect the tolerance and patient compliance. Even the more stable, synthetic 3rd generation retinoids, such as adapalene, trigger adverse effects such as erythema, scaling, dryness, pruritus, and burning in 10-40% of patients. Without providing a clear activity gain, better teratogenic profile is their only advantage over the earlier retinoids. Here, we propose to develop a functional analogue of retinoids (named SBD.073), which has been isolated from a traditional medicinal plant used for psoriasis and which has been extensively characterized by our lab in terms of its safety, adverse skin effects as well as skin-normalizing bioactivity, as compared to retinol. From these studies it appears that not only SBD.073 is not a skin irritant, but it protects skin from UV-induced erythema (without being a sunscreen) - an important clinical finding in view of retinoids being used in conjunction with phototherapy. Accordingly, our other clinical case study established SBD.073 to be non-phototoxic. Furthermore, this retinoid analogueis not mutagenic and has better anti-inflammatory properties than retinol, while it retains powerful retinol-like activities - so important in psoriasis treatment - such as the abilit to induce cell differentiation and normalize skin structure by strengthening the dermo- epidermal juncture (basement membrane). Hence, it is reasonable to hypothesize that this compound could be better than any current retinoid treatment for the topical treatment of psoriasis. Here, we propose to test this hypothesis by comparing the activity of SBD.073 to the current topical retinoid therapies in several safety and bioactivity models relevant to psoriasis. This will includ tests on tridimensional skin substitutes stimulated with pro-inflammatory cytokines, 2 mouse models of psoriasis with complementary psoriasis-relevant phenotypes, 1 model of retinoid-induced teratogenicity, as well as phototoxicity and skin irritation tests. If successful, this proect will identify the first bioactive retinoid analogue with skin-protective activity, opening the doorto a new generation of functional retinoids


Compositions and methods for treating angiogenesis-related diseases and for skin care in mammals is disclosed that includes, as an active pharmaceutical agent, an effective amount of purified extract from Angelica sinensis, or a fraction or a lyophilizate thereof, or one or more active component contained in said extract.

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