Abstract: It is well known that terrestrial environments host immense microbial biodiversity. Exposed to different types of stress, such as UV radiation, temperature fluctuations, water availability, and the inter- / intra-specific competition for resources, terrestrial microorganisms have evolved to produce a large spectrum of bioactive molecules. Bacteria, archaea, protists, fungi, and algae have shown a high potential for producing biomolecules for pharmaceutical or other industrial purposes as they combine a sustainable, relatively low-cost, and fast-production process. Herein, we provide an overview of the different bioactive molecules produced by terrestrial microorganisms with skin-protecting applications. The high content in polyphenolic and carotenoid compounds produced by several strains and the presence of exopolysaccharides, melanins, indole and pyrrole derivatives, cyclosporine, carboxylic acids, and other molecules, are discussed in the context of their antioxidant, photo-protective and skin-whitening activity. Relevant biotechnological tools developed for the enhanced production of high-added value natural products, as well as the protecting effect of some antioxidant, hydrolytic, and degrading enzymes, are also discussed. Furthermore, we describe classes of microbial compounds that are used or can potentially be used as antimicrobials, moisturizers, biosurfactants, pigments, flavorings, and fragrances. 

Click on Cistanche Tubulosa Supplement

For more info: 

david.deng@wecistanche.com  WhatApp:86 13632399501

According to relevant studies,cistanche is a common herb that is known as "the miracle herb that prolongs life". Its main component is cistanoside, which has various effects such as antioxidant, anti-inflammatory, and immune function promotion. The mechanism between cistanche and skin whitening lies in the antioxidant effect of cistanche glycosides. Melanin in human skin is produced by the oxidation of tyrosine catalyzed by tyrosinase, and the oxidation reaction requires the participation of oxygen, so the oxygen-free radicals in the body become an important factor affecting melanin production. Cistanche contains cistanoside, which is an antioxidant and can reduce the generation of free radicals in the body, thus inhibiting melanin production.

1. Introduction 

Microorganisms are extremely diverse organisms, including bacteria, archaea, protists, fungi, and algae. In recent decades, there has been great progress in exploiting the immense chemical diversity available from the abundant microbial world [1,2]. After the discovery of the fungal metabolite penicillin in 1928, which was the beginning of the golden age of microbial-derived natural products and pharmaceuticals, treatments for fungal and parasitic infections as well as for several types of cancers followed [3]. In the forties and early fifties, almost all groups of important antibacterial antibiotics (tetracyclines, cephalosporins, aminoglycosides, macrolides) were discovered, while in the fifties and sixties, antitumor, antiviral, and non-antibiotic-enzyme-inhibitory-metabolites were isolated, mainly from Streptomyces species [4]. 

Among the various environmental factors affecting skin homeostasis, ultraviolet (UV) irradiation is the most dangerous component, as it can cross the epidermis and reach the upper dermis. Additional parameters that affect all skin layers and thus contribute to skin aging are dietary (e.g., high-fat diet) and lifestyle habits (e.g., smoking), various air pollutants, as well as internal factors such as metabolism, hormones, inflammatory processes, etc. [7–9] (Figure 1). Damaging agents modulate numerous molecular events and signaling pathways that (among others) lead to mitochondrial dysfunction, increased genome, and proteome damage; increased synthesis and activity of matrix metalloproteases, decreased collagen production, triggering of stress-induced premature senescence (SIPS) and accumulation of the inflammatory senescence-associated secretory phenotype (SASP) [8–11]. The maintenance of a highly effective intra- or extracellular defense system capable of protecting against the adverse effects of irradiation and other stressors is crucial for safeguarding skin homeostasis. Adverse effects are macroscopically characterized by the loss of skin tone and an increase of wrinkles, dehydration (due to increased epidermal thickness), hyperpigmentation, and sallowness (yellowing or pale tinted skin) (Figure 1). 

Despite the large number of individual studies and evidence for the potential use of terrestrial microorganisms in the fast-growing cosmetic sector, so far no systematic review has addressed their applications. It is worth mentioning that the global market for cosmetic and cosmeceutical products was valued at USD 532.4 billion in 2017, and is expected to reach a market value of USD 805.6 billion by 2023, registering a CAGR (Compound Annual Growth Rate) of 7.14% during 2018–2023 [12]. 

In the current study, we provide an overview of the different bioactive compounds with skin-protecting effects (and thus of cosmetic and cosmeceutical interest) isolated, from a broad range of terrestrial microorganisms including bacteria, algae, fungi, and protists. Examples of biomolecules with skin-protecting interest that are heterologously produced and/or biotransformed are included. The term “terrestrial” encompasses microorganisms from soil and freshwater, plant endophytes, and lichens. Marine microorganisms and mushrooms (all Basidiomycota and Ascomycota) are excluded, as they have been recently reviewed [2,13]. Representative bioactive compounds from terrestrial microorganisms with antioxidant, photo-protective, and skin-whitening activity, along with antimicrobial and moisturizing agents, pigments, fragrances, and flavors are discussed. A detailed table including bioactive molecules, the source organisms, their habitat, and the biological activity and their presence in the list of cosmetic substances and ingredients of the European Union (CosIng inventory [14]) is provided.

2. Antioxidants

Oxidative stress is one of the prevailing causes of skin aging due to increased production and/or accumulation of Reactive Oxygen (ROS) and Nitrogen Species (RNS). The imbalance between their production and the endogenous antioxidant defense mechanisms may result in cellular oxidative stress, causing wrinkling, drying, photo-aging, pigmentation, and elastosis of the skin. In addition, the accumulation of free radicals may be responsible for cutaneous inflflammation and skin cancer [15]. 

Reactive oxygen species (ROS) are formed as either by-product of normal metabolism (e.g., mitochondrial oxidative phosphorylation), as well by NAD(P)H oxidases, or by exogenous sources such as atmospheric pollutants, UV light, X- or gamma-rays [16]; if their concentration exceeds the cellular antioxidant capacity, ROS cause oxidative stress and damage to all cellular biomolecules [10]. 

Topical antioxidant products could act as scavengers of reactive species, inhibiting the initiation of chain reactions, responsible for cellular oxidative stress [17]. Many reports have demonstrated the ability of marine microorganisms to biosynthesize antioxidant compounds [2]. Concerning terrestrial microbes, compounds with a signifificant inhibition of oxidation reactions, like polyphenols, carotenoids, or exopolysaccharides, are extensively discussed in the following sections.

Bioassays involving the neutralization of different radicals such as the stable radical 2,2-diphenyl-1-picrylhydrazyl (DPPH), the cation radical 2,20 -azino-bis-3-ethylbenzotiazolin-6-sulfonic acid (ABTS), as well as the hydroxyl and nitric oxide radicals are widely applied for determining the in vitro antioxidant potential. Even if the relation to the in vivo antioxidant effiffifficacy was not clearly described, the measured antioxidant activity can give an estimation of the amount of the compounds that can be oxidized under conditions of the assays [18]

2.1. Phenolic Compounds

Phenolic compounds are well known for their strong antioxidant and radical scavenging activity, as well as for their interaction with different pharmacological targets. The strong correlation between the microbial phenolic content and the antioxidant activity has been shown by several authors using different microorganisms. Huang et al. confirmed this positive correlation during their investigation of fungal endophytes isolated from medicinal Chinese plants [19]. The strong contribution to the antioxidant activity was also confirmed in Aspergillus austroafricanus, an endophytic fungus isolated from Zingiber offiffifficinale rhizome. HPLC analysis of the crude extract showed mainly the presence of hydroxycinnamic acids such as ferulic acid (1), p-coumaric acid (2), and cinnamic acid (3) [20] (Figure 2). Those molecules are well-known in the plant kingdom and have been extensively studied for their antioxidant capacity (Table 1).

Similar conclusions were drawn using cultures of the microalgae Arthrospira platensis [21] and of other Arthrospira sp. [22,23]. Simple phenolics and hydroxycinnamic acids, such as gallic acid, chlorogenic acid, ferulic acid, and caffein acid have been isolated from different species of microalgae e.g Chlorella vulgaris, Haematococcus pluvialis, Diacronema lutherie, Phaeodactylum tricornutum, Tetraselmis suecica, Ankistrodesmus sp., Spirogyra sp., Euglena cantabrica, Caespitella patchier, and Porphyridium purpureum [24–26].

Studies on terrestrial cyanobacterial species from the genera Anabaena, Nostoc, Nodularia, Microcheate, Oscillatoria, Synechocystis, Hapalosiphon, Mastigocladus, Scytonema, Westiellopsis, Cylindrospermum, Aulosira, Chroococcus, Lyngbya, Calothrix, Dichothrix, Phormidiochaete, Limnothrix, and Phormidium have also reported the correlation of their antioxidant activity with their total phenolic content. Chlorogenic and gallic acid were identified as the main phenolics in several cyanobacterial species, with Dichothrix sp. being one the most efficient producer of those compounds (77.9 µg/g and 24.4 µg/g fresh weight, respectively) [26]. 

Resveratrol (4), another well-known natural compound produced by plants, has recently been reported from endophytes isolated from grapevine varieties [27,28]. It is considered one of the most famous compounds for its unique anti-aging properties (Figure 2). It has been widely reported to be a strong inhibitor of ROS production and protein oxidation and a more effective agent than vitamins E and C against lipid peroxidation [29]. Microorganisms have been successfully considered for the production of resveratrol since their synthesis and/or extraction from plants is considered inefficient due to high requirements of organic solvents, biomass, and low final yield. Resveratrol was first industrially produced in 2009, using Saccharomyces cerevisiae. Since this development, different methods such as bioconversion and genetic engineering have been used to obtain higher yields. For instance, resveratrol has been produced by Alternaria sp. (1.4 µg/L), and by genetically modified S. cerevisiae (531.4 mg/L), and E. coli (2370 mg/L) [30]. The molecules discussed, as well as additional microbial phenolic compounds that have antioxidant or other related biological activities, are presented in Table 1.

For more info: david.deng@wecistanche.com  WhatApp:86 13632399501