Cortico-steroids were introduced into medicine around 50 years ago and have become one of the classes of drugs most prescribed by doctors world-wide. The efficacy of topical cortico-steroids in the treatment of symptoms related to flare-ups of the immune system and of inflammation is very well-known and practically indisputable. That said, some inherent aspects of adverse reactions to this class of drugs on the skin should be taken into consideration. Among these are immunosuppression, a reduced cellular turnover, tissue atrophy, degradation of the extracellular matrix, dryness and, as a consequence, premature and/or exacerbated aging. The corticoid-like action shows the solution to adverse reactions, in that the active ingredient has important biological effects similar to those of cortico-steroids, yet without causing the adverse or secondary effects common to cortico-steroids.

When human skin ages, each of its layers undergoes several biological changes. Cutaneous aging is a multifactorial and progressive degenerative process, one which is inevitable and practically irreversible. It is the result of two synergetic processes of aging: intrinsic or chronological aging and extrinsic or photo-aging. 

Macroscopically speaking, intrinsic aging leads to considerable changes, including dermal atrophy, wrinkles, dryness, and loss of elasticity and subcutaneous fat. The severe appearance of this process is in its turn due to the drastic histological changes represented mainly by deep atrophy of the dermal framework, with reduction in the number and function of fibroblasts, and destruction of the important protein structures – especially collagen and elastin. There is also an alteration in the proliferative cellular homeostasis, resulting in lesions which are very often malignant or irreversible. Beyond this, there is a reduction in the number and size of epithelial cells, which could compromise protection, excretion, absorption, thermoregulation, pigmentation, sensory perception and regulation of immunological processes. With aging, keratinocytes and fibroblasts decrease in number and are less able to produce responses to the different growth hormones and factors. 

With photo-aging, the surface of the skin becomes dry, with many, many blotches and deep wrinkles. Histologically, photo-aged skin experiences changes in keratinocytes, and a reduced size of melanocytes, which grow in number and are distributed irregularly. Wrinkles, the clearest sign of skin aging, are formed by a combination of factors, including repetitive muscle movements, smoking, and dehydration. Visual clinical comparisons between areas of skin exposed to UV radiation with and without sunscreen show that the main changes in the appearance of skin related to cutaneous aging occur primarily from sun exposure. A main aspect of photo-aging is the involvement of heat, caused in part by UV radiation, but strongly attributed to infrared spectrum radiation. Heat is in its turn the main stimulus for the increased expression of matrix metalloproteinases enzymes (MMPs) and reactive oxygen species (ROS), along with the production of inflammatory mediators in the skin. These include proinflammatory cytokyines, angiogenic and transcription factors, serine proteases and signalling pathways, which culminate in the degradation of the extracellular matrix and in the many signs of photo-aging. The figure below shows the cascade of symptoms brought about by sun exposure and the consequences of thermo-aging on the skin. 

The Mechanism of Thermo-Aging on the Skin. 

Heat

Cytokine production

Vasodilation and angiogenesis

Serine proteases

Inflammation

Reduction in collagen-binding proteins 

Collagen deficiency (wrinkles) 

Actinic elastosis (loss of elasticity) 

Thermo-Aging on the Skin

Physalis Angulata is a vegetable-origin active ingredient obtained via supercritical fluid extraction from Physalis Angulata, a species native to Brazil. It is extremely efficacious as corticoid-like due to its immense immunomodulating and its ‘anti-photo-aging’ properties. Further, it increases serine proteases, maintaining and repairing skin collagen. 

The active ingredient’s efficacy was proven in in vitro tests comparing it with hydrocortisone. The same antihistamine results were gleaned, with a reduction in proinflammatory cytokines (IL1-alfa, TNF-alfa, IL6-alfa, IFN-γ), inflammation mediators and related enzymes (PGE2, LTB4, PA2, LOX and COX-2), while the active ingredient doesn’t have the collateral effects common to cortico-steroids, such as immunosuppression (IL-10) or reduced tissue growth factor (TGF). 

In addition, the active ingredient decreases intradermal microinflammation, regulates intradermal temperature, providing protection against infrared rays and visible light, and increases pro-collagen, collagen I and GAGs.

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