Research Progress on Skin Aging and Active Ingredients
Abstract
:1. Introduction
2. Mechanisms of Skin Aging Processes
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- Free radicals and oxidative stress theory
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- Inflammation theory
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- Photoaging theory
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- Nonenzymatic glycosyl chemistry theory
3. Research on Skin Anti-Aging Compounds
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- Data from clinical studies on human subjects:
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- Ceramide: Ceramide has a protective effect on the skin from external pressure, which can prevent skin dryness and play a role in the skin barrier [42]. A group of 30 healthy adults (including women and men) aged 20 to 60 years old were selected and they consumed dietary supplements (including 1197 mg of acetic acid bacteria containing 9.06 mg of ceramide) for four consecutive weeks. Physical measurements, blood tests, and urine analyses showed that ceramide can preserve the skin barrier [43]. This reveals that ceramide has a role in protecting the skin and resisting the influence of external substances on skin aging.
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- Retinol: Retinol can significantly improve the microenvironment of dermal ECM, stimulate skin cells to produce ECM (e.g., type I collagen, fibronectin and elastin), can promote the formation of dermal blood vessels, and can stimulate TGF-β/CTGF, which is the main regulatory factor for maintaining an ECM steady-state [44]. Women (n = 24) aged 18–65 with acne, pigmentation, or melasma were selected and they applied a 3% retinol for six consecutive weeks. The results showed that the skin of the subjects showed significant improvements in fine lines, wrinkles, pore size, relaxation, pigmentation spots, clarity, brightness, and overall light damage [45]. This indicates that 3% retinol is an effective drug for treating skin aging.
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- Hyaluronic acid: The most obvious clinical feature of photoaging is the appearance of wrinkles, and the tissue feature is the accumulation of abnormal elastin in the dermis and a serious loss of collagen fibers. The integrity of elastin and collagen fibers in the dermis is maintained by their interaction with hyaluronic acid and a proteoglycan network structure; therefore, hyaluronic acid degradation may be the initial process before the decomposition of fibril components [46]. Female subjects (n = 60) with skin aging were selected to participate in clinical trials, taking 200 mg of hyaluronic acid orally, daily, for 28 consecutive days. After 28 days, the skin wrinkles and moisture content of the subjects were tested, and the results showed that hyaluronic acid can increase the skin moisture content, reduce the wrinkle depth, and increase the skin elasticity and strength [47]. This reveals that hyaluronic acid has the effect of improving skin aging.
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- Astaxanthin: Astaxanthin has antioxidant and anti-inflammatory effects, and it can reduce skin photoaging [48]. Astaxanthin is related to a variety of anti-inflammatory mechanisms, including PI3k/Akt, Nrf2, NF-κB. Erk1/2, JNK, p38 MAPK and jak-2/stat-3 [49]. Healthy female subjects (n = 23) were selected to take orally astaxanthin capsules containing 4 mg for 10 weeks. The skin erythema dose, skin water content and other parameters of the subjects were measured. The results showed that the astaxanthin-administration group had a reduced skin moisture loss, an improved skin roughness, and that skin degradation caused by UV light was prevented [50]. This revealed that astaxanthin has the effect of improving skin aging.
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- Collagen tripeptide (Gly-Pro-Hyp): Collagen derived tripeptide (Gly Pro Hyp) can prevent a reduction in the extracellular matrix (ECM)-related genes COL1A, elastin and fibronectin [51]. Female subjects (n = 64) were randomly and double-blind selected, to take 1000 mg of Gly-Pro-Hyp orally once a day for 12 weeks. After 12 weeks, the skin moisture content, wrinkles, and elasticity of the subjects were tested. The results showed that compared with the control group, the skin moisture content of the subjects in the treatment group increased, wrinkles decreased, and elasticity improved [52]. This reveals the role of Gly-Pro-Hyp in skin anti-aging.
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- Acetylzinc ketone (AZ): Acetylzinc ketone (AZ), a derivative of zinone and a phytochemical in ginger, is a new compound with a photoaging effect. AZ can increase the expression of the Notch pathway genes, reduce MMP-1, MMP-3, and MMP-12, and can also reduce the expression of the reactive oxygen species-related genes PMAIP1 and arg2 [53]. Healthy female participants (n = 31, aged 44 ± 7 years) were randomly selected and smeared twice a day for 8 weeks. Facial image analysis photography and software were used to evaluate the signs of photoaging, including wrinkles, pigmentation and redness. The results showed that compared with the control group, the average wrinkle severity, total wrinkle volume, pigment intensity and redness intensity of subjects in the administration group were significantly reduced within 8 weeks [54]. This indicates that AZ plays a significant role in resisting skin aging.
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- Epigallocatechin Gallate (EGCG): EGCG has strong antioxidant activity and can significantly reduce intracellular reactive oxygen species [55]. Female healthy subjects (n = 88) were selected and supplied with Hanhoo cosmetics (i.e., Hanhoo organic tea stamen whitening water, with 30 mL of Hanhoo organic tea stamen extremely tender essence, and Hanhoo organic tea stamen tender white emulsion or whitening cream) containing epigallocatechin gallate EGCG for 12 weeks, which was applied by smearing the skin of the subjects. The results showed that the EGCG components could have scavenged ROS in the subjects, thus preventing DNA damage caused by UV light [56], with the effect of resisting skin aging.
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- Vitamin C: Vitamin C is a nutrient necessary for a variety of biological functions. It is a scavenger of reactive oxygen species [57] and has the effect of preventing lipid peroxidation. Using a cosmetic containing 20% vitamin C, 50 randomly-selected female subjects were tested. The vitamin C was applied to their face every day. The skin melanin index, elasticity, gloss, moisture, smoothness, roughness, scaliness and wrinkles were detected at the 4th and 8th weeks. The results showed that vitamin C could improve the color, elasticity and luster of the skin [58]. This suggests that vitamin C has a potential anti-skin aging effect.
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- Melatonin: The indolic hormone melatonin, which is widely present in various tissues including the skin, regulates circadian rhythms and promotes sleep. Melatonin can penetrate membranes and mitigate lipid peroxidation and protein oxidation, as well as oxidative damage to the mitochondria and DNA caused by UVR [59]. In a randomized, split-face, assessor-blinded, prospective 3 month study, 22 women (mean age 55 years) with moderate to severe skin aging applied melatonin-based creams to their faces. The melatonin-based creams significantly improved the skin tonicity and skin hydration with a significant reduction in the skin roughness [60]. This suggests the skin anti-aging effect of melatonin.
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- Protocatechuic acid: Protocatechuic acid has antioxidant and anti-inflammatory effects. This is caused by Akt, mTOR, and NF-κB in HaCaT cells and the primary keratinocytes pathway plays a role, which is also regulated by JNK and p38 MAPK [61]. Female subjects (n = 22) applied 0.02% protocatechuic acid for 8 weeks to address facial wrinkles, crow’s feet around the eyes, and other MMP-1 secretions. The results showed that protocatechuic acid could inhibit MMP-1 produced by irradiation and inhibit the percentage of skin wrinkles [62]. This revealed that protocatechuic acid has the effect of skin anti-aging.
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- Nature-Based bakuchiol: Natural bakuchiol has a strong antioxidant activity, which can significantly reduce the levels of PGE2 and MIF [63]. Female subjects (n = 60) with sensitive skin (e.g., eczema, blackheads, and cosmetic intolerance) were selected and they applied cosmetics containing natural bakuchiol according to the needs of the face for 4 weeks. The smoothness, gloss and overall appearance of a subject’s skin after 4 weeks were detected, and the results showed that natural bakuchiol had a therapeutic effect on patients with sensitive skin [64]. This suggests that natural bakuchiol has certain anti-aging effects on the skin.
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- Rhamnose: Rhamnus can inhibit the generation of AGEs and the expression of MMP-9 [65,66]. Healthy women (n = 20) aged 50–68 were selected as participants, and a 5% rhamnose emulsion with a 5% was applied, twice a day, to the forearms of each participant for 8 consecutive weeks. The results showed that rhamnose can promote an increase in the skin epidermal thickness and collagen production [67]. This indicates that rhamnose has the potential to improve skin aging.
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- Timosaponin AIII (TA-III): Timosaponin A-III are steroidal saponins extracted from the traditional Chinese medicine, Anemarrhena asphodeloides, which has anti-inflammatory activity [68]. Moreover, the transcriptional levels and protein expressions of cyclooxygenase-2 (COX-2) and MMP-9 induced by UVB were inhibited in a dose-dependent manner. The TA-III inhibited UVB-induced protein kinase (MAPK) signaling, protein-1 (AP-1), and nuclear factor κB (NF-κB) activation, thereby preventing a TNF-α overexpression of interleukin-6 (IL-6) and COX-2 in human epidermal keratinocytes [69]. Female subjects (n = 21) aged between 43 and 55 years old, who had begun to form or had already-formed wrinkles and who met the selection criteria of subjects were selected, and the agent containing 0.25% of TA-III was applied for 12 weeks. The results showed that wrinkles were significantly reduced, and that secreted MMP-1 was reduced, which had the effect of resisting photoaging [70]. This revealed that the TA-III had the effect of treating skin aging.
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- Poly L lactic acid (PLLA): PLLA not only supports an increase in HIF-1α but also promotes collagen synthesis [71]. Healthy women (n = 40) were selected randomly and received treatment three times every 4 weeks. They were injected with PLLA on both sides of the face (prepared in a 1:1 dilution ratio of sterile water and PLLA), with 5 to 6 mL on each side. A test was conducted after completion of the experiment. The results showed that the PLLA treatment group showed an increase in skin elasticity and moisture content, a decrease in skin epidermal moisture, and a significant reduction in pigmentation, erythema, and pore size [72]. This indicates that PLLA has an anti-aging effect on the skin.
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- 10-Hydroxystearic Acid (10-HAS): 10-HSA is the most effective PPAR α Agonist, and it increases the level of type I collagen in primary human fibroblasts [73]. Forty-two Caucasian women with Fitzpatrick skin types II-III were treated with 1% (33 mM) HSA twice daily for 8 weeks. The results showed that 10-HSA can reduce the expression of the aging protein p53, inhibit the expression of the MMP-1 gene, reduce the pigmentation of senile plaques, and improve the coarseness of pores [74]. This reveals the anti-aging effect of 10-HSA on the skin.
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- Glycolic acid (GA): GA can reduce UVB-induced cellular inflammation and aging, regulate the expression of MMPs and collagen, and reduce the expression level of MMP-9 induced by UV. GA can be more widely used for photoaging and inhibit the formation of wrinkles [75]. A total of 262 randomly-selected healthy women aged 30 to 60, with moderate to late stage photoaging skin, and a 70% glycolic acid facial peel was applied on their faces. After 14 days of the experiment, it was found that the subjects who applied glycolic acid had a better skin tolerance and resulting cosmetic effects compared to those who did not apply glycolic acid [76]. This reveals that organic acids such as glycolic acid may have anti-aging and skin condition-improving effects on the skin.
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- Data from Animal experiments:
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- Bavachalcone: Bavachalcone is a prenylchalcone that is the major bioactive chalcone isolated from Psoralea corylifolia [77,78]. The experiment was conducted using WT and TET3+/− C57BL/6J mice, where paraquat (at 10 mg/kg, with a dosage volume of 0.1 mL/10 g mouse body weight) was intraperitoneally injected for modeling and administration. The paraquat treatment was carried out from the sixth week until the fortieth week, while simultaneously, bavachalcone (at 20 mg/kg, with a dosage volume of 0.05 mL/10 g mouse body weight) was administered by gavage. The results showed that, in comparison with the control group, the activity of SOD in the skin tissue of mice in the treatment group was lower; the MDA levels decreased; the activity of catalase (CAT) increased; and the content of Hyp increased [77,79]. This reveals that bavachalcone has an anti-aging effect on the skin.
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- Banana peel polyphenols (BPP): Banana peel polyphenols have antioxidant effects [80], and an experiment was carried out with rats where the model was made by a subcutaneous injection of 300 mg/kg d-galactose for 7 weeks. An amount of 120 mg/kg BPPs was administered by gavage for 7 weeks. An analysis of the experimental results showed a significant increase in the content of type I and II collagen in the skin tissue, a decrease in the expression level and protein content of MMP-1, and an increase in the expression level and protein content of the AQP gene [81]. This indicates that BPPs have a therapeutic effect on skin aging.
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- Curcumin: Curcumin is a component of curcuma [82]. Curcumin can block the signal pathway of light damage, and it has the effect of resisting oxidative stress and inhibiting inflammation [83]. BALB/c-nu/nu mice were used to construct a skin aging model, and 125 mg/kg/d d-galactose was injected subcutaneously to create this skin aging model for 21 consecutive days. After modeling, 80 mg/kg of curcumin was administered by gavage for three consecutive weeks. After the experiment, the results for a skin tissue detection showed an increase in the SOD activity and Hyp content accompanied by a decrease in the MDA content [84,85]. This study demonstrates that curcumin can significantly affect skin aging-related indicators. Moreover, it has the ability to resist skin aging.
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- Procyanidins: Procyanidins have therapeutic potential for photoaging, with antioxidant and anti-inflammatory effects, and they can inhibit the expression of MMPs induced by UVB [86]. Kunming female mice were injected with 5% d-galactose 10 mL/kg subcutaneously every day, UV radiation exposure was conducted the next day, and then 50 and 100 mg/kg of procyanidins were administered by gavage for 30 consecutive days. An analysis of the skin tissue indicators showed a decrease in the MDA levels; and an increase in the SOD value and GSH-Px activity and inhibiting oxidative damage [87,88,89]. The results imply that procyanidins have therapeutic effects on skin aging.
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- Resveratrol: Resveratrol is a polyphenolic compound that has therapeutic effects on skin photoaging. It exerts anti-aging effects on the skin through various pathways such as MAPK, MAPKK, FOXO3, TGF, or MMP-1 [90]. Using adult Wistar female rats, bilateral ovaries were excised to reduce the secretion of estrogen, and a skin aging model was constructed. Resveratrol was administered orally at doses of 10, 30, and 60 mg/kg for 31 consecutive days to detect skin tissue indicators. The results showed an increase in the SOD and hydroxyproline (Hyp) contents, a decrease in the malondialdehyde (MDA) content, and an increase in the SIRT1 protein content [91], indicating that resveratrol has an anti-aging effect on the skin. In addition, studies have shown that resveratrol also has an anti-scar formation effect [92].
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- Codonopsis pilosula polysaccharides (CPP): Codonopsis pilosula polysaccharides are one of the main active ingredients of Codonopsis pilosula. Codonopsis pilosula polysaccharides have antioxidant, anti-inflammatory and anti-aging effects [93]. This experiment was conducted on mice. The model was made by a subcutaneous injection of a 5% d-galactose solution 1 g/kg for 42 consecutive days, and Codonopsis pilosula polysaccharide of 50 mg/kg and 150 mg/kg was administered by gavage for 32 consecutive days. An analysis of the skin tissue indicators showed a decrease in the MDA levels [93,94]. This implies that CPPs have anti-aging effects on the skin.
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- Lycium barbarum polysaccharide (LBP): LBP is a natural polysaccharide extracted from Lycium barbarum, which has anti-inflammatory, anti-apoptotic, and anti-aging effects. Its main effects include reducing ROS and MDA while increasing SOD in the body [95]. These effects are essential for the resistance of photoaging [96]. This experiment was conducted with mice, and the skin aging model was established by a subcutaneous injection of 1000 mg/kg/d d-galactose for 42 consecutive days. Low, medium, and high doses of 5, 10, and 20 mg·kg-1·d-1 were administered by gavage. A daily dosage of 20 mL per kilogram of mouse weight was administered for 42 consecutive weeks. After 42 days, the SOD activity and GSH-Px activity in the skin tissue of the mice were significantly increased. Studies have shown that MDA is an important indicator for detecting skin aging, exhibiting a decrease in the MDA content and an increase in the Hyp content [97,98]. This indicates that LBP can resist skin aging.
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- Saussurea Medusa Maxim Polysaccharides (SMMP): Saussurea Medusa Maxim Polysaccharides have anti photoaging effects [99]. This experiment was conducted on mice. The model was created by subcutaneously injecting d-galactose and subjecting the mice to 5% UVB radiation, with a daily dose of 10 mL/kg of D-galactose. The model was established for 40 consecutive days, and starting from the 11th day of the experiment until the end, the mice were administered 4 g/kg/d SMMPs by gavage. After the completion of the modeling, the indicators of skin tissue were tested, and the results showed a significant increase in the SOD activity, GSH-Px activity, and Hyp activity, but they showed a decrease in the MDA content [100]. This indicates that SMMPs have anti-skin aging effects.
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- Pyrroloquinoline Quinone (PQQ): PQQ has an inhibitory effect on the secretion of MMPs and can prevent a decrease in collagen synthesis [101]. Wild-type mice (WT) and Bmi-1 gene knockout homozygotes were utilized to create a mouse model. The Bmi-1 gene, associated with aging, was knocked out to induce the aging phenotype. An amount of 4 mg of PQQ was added to each kilogram of feed and raised for 4 weeks. The experimental results showed an increase in collagen, and enhanced skin cell proliferation, reduced skin tissue fibrosis, cleared oxygen free radicals, and decreased ROS levels [102]. This indicates that PQQ has an anti-aging effect on the skin.
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- l-linalool: l-linalool has sedative and anxiolytic effects [103]. Female mice of a healthy Swiss species (ICR strain) were injected subcutaneously with 1.5 mg/g/d d-galactose for the construction of a skin aging model for 30 consecutive days. An amount of 5.0% of l-linalool was administered to the skin tissue. The skin tissue indicators were detected, and the results showed that the SOD increased, MDA decreased, skin moisture increased, Hyp content increased, oxygen free radicals were eliminated, and lipid peroxidation was reduced [104]. This indicates that the drug has anti-aging effects on the skin.
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- β-Nicotinamide Mononucleotide (NMN): NMN is currently a component that can treat oxidative stress-induced skin aging [105]. This experiment involved the construction of a mouse model of photoaging, exposing the mice to UVB radiation. The skin’s oxidative damage was induced using UVB (400 nm), and the mice were subjected to 12 h of UVB irradiation per day for 1 week. The use of 300 mg/kg bw of NMN was used for intraperitoneal injection for three consecutive weeks. The experimental results indicated that NMN can reduce inflammatory factors (e.g., TNF-α, IL-1 β, IL-6, etc.) and improve SOD levels. This indicates that NMN has a therapeutic effect on skin aging [106].
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- Quercetin: Quercetin is a natural polyphenol with antioxidant and anti-inflammatory effects, which can inhibit the expression of MMP-1. Quercetin significantly inhibits the activity of AP-1 and NF-κB nuclear factors induced by ultraviolet radiation. It can directly target PKCδ and JAK2 in the skin, and it has a protective effect on UV-mediated skin aging and inflammation [107]. Male Kunming mice were injected with d-galactose at a concentration of 200 mg/kg/day for 8 weeks, and 10–20 mg/kg/day quercetin was injected subcutaneously for 8 weeks. By detecting a degree of looseness and roughness of the skin, a thickening of the epidermis and dermis, an increased collagen content, a decreased expression of aging proteins, and an increased superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px) [108], the study demonstrated that quercetin has an anti-aging effect on the skin.
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- Vitamin E: Vitamin E is an efficient antioxidant that can resist skin photoaging, inhibit the production of oxygen free radicals, and protect the skin from the adverse effects of photoaging. Vitamin E is a positive drug that inhibits skin oxidative aging. This experiment involved homogenizing Hainan pig skin and subsequently adding 20–100 μL of vitamin E (≥98%) for 1 h of a dark reaction. The results indicated a significant increase in both the SOD activity of the skin tissue and CAT activity; it also showed a reduction in the content of protein oxidation products caused by hydrogen peroxide [109]. This demonstrates that vitamin E has an anti-aging effect on the skin.
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- Chitosan: Chitosan can resist oxidation and inflammation, maintaining the form and level of collagen [110]. Experiments were conducted using rats where chitosan solution with a mass fraction of 1% was applied daily. The results showed an increase in the Hyp content in the skin tissue and a denser collagen fiber [111,112]. Hyp is a unique amino acid for synthesizing collagen, indicating that chitosan can promote skin firmness and have anti-aging effects on the skin.
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- Ganoderma lucidum polysaccharides (GLP): Ganoderma lucidum polysaccharides are natural antioxidants with no toxic side effects, which can counteract the B-induced photoaging of fibroblasts. Ganoderma lucidum polysaccharides can inhibit the production of ROS [113]. This experiment was conducted on mice, and the model was made by a subcutaneous injection of 1000 mg/kg/d d-galactose for 42 consecutive days. A daily dosage of 0.5% ganoderma lucidum polysaccharide was applied to skin tissue for 42 consecutive days. After the completion of the modeling the relevant indicators of skin tissue were tested, and the results showed that ganoderma lucidum polysaccharides can eliminate oxygen free radicals, reduce the MDA content, improve the SOD activity and increase the Hyp content of collagen [114]. This reveals that Ganoderma lucidum polysaccharides can resist skin aging.
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- Wax gourd polysaccharides (WGP): Wax gourd polysaccharides have antioxidant effects and can scavenge oxygen free radicals [115]. This experiment was carried out on mice. The model was made by administering 500 mg/kg/d d-galactose for 6 weeks, and then the skin tissue was smeared with 5 mg/mL of wax gourd polysaccharide every day, using 2 mL every day, for 6 weeks. After 6 weeks of administration, the WGPs had the ability to scavenge hydroxyl radical and superoxide anion radicals; moreover, at 2 mL, it had an inhibitory effect on tyrosinase. After testing the skin tissue-related indicators, the SOD activity and CAT activities increased while the MDA content decreased [116]. This indicates that WGPs have anti-aging effects on the skin.
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- Hydroxyacetic acid: Hydroxyacetic acid has the effect of slowing down skin aging, reducing cellular inflammation caused by UVB, resisting photoaging, and inhibiting the expression of MMP-9 [50]. Kunming mice were injected subcutaneously with 1 mg/g/d d-galactose for 12 weeks. Hydroxyacetic acid with concentrations of 20%, 35%, 50%, and 70% was applied every 2 weeks for administration. The relevant indicators of the skin tissue were tested, and the results showed an increase in collagen and elastic fibers [75,117]. This indicates that HA has a certain effect on resisting skin aging.
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- Data from experimental studies on cell cultures:
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- GX-50: GX-50 is an extract from Zanthoxylum bungeanum [119]. Primary human skin fibroblasts were utilized for this modeling, with a treatment involving 50 μM of hydrogen peroxide. The treatment was administered once every two days, totaling four times. GX-50 was also administered once every two days for a total of four times. After the experiment, an analysis of a β-Galactosidase staining test showed that the positive rate was reduced and the MDA content or ROS level was decreased [120]. This indicates that GX-50 has a certain therapeutic effect on skin aging.
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- Ligustrazine: Ligustrazine has good antioxidant activity and has the potential to treat skin aging caused by ultraviolet radiation [121]. Using UVA irradiation, human skin fibroblasts were used to create a skin aging model, using 10 J per day for five consecutive days, where a ligustrazine hydrochloride injection (2 mL:40 mg) was administered for the five consecutive days. The pharmacological effect of the ligustrazine on skin aging was tested, and the results showed that the positive rate of β-galactosidase staining was decreased, the total amount of ROS was decreased, the expression level of the p53 protein was decreased, and the mRNA expression levels of MMP-1 and MMP-3 were decreased [122]. The experimental results indicate that ligustrazine has an anti-aging effect on the skin.
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- Caffeic acid phenethyl ester (CAPE): CAPE is the active ingredient of propolis [123]. Human dermal fibroblasts (HDF) were selected and used to construct an aging model using ultraviolet radiation. The results of administering CAPE showed that CAPE can inhibit the expression of MMP-1 in human skin cells, and the pathway of action occurred when the CAPE inhibited lysine acetylation induced by UV in human skin tissue [124]. This reveals that CAPE has the effect of resisting skin aging.
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- Total flavonoids of Eurasian Convolvulus: A skin aging model was induced using mouse skin fibroblasts and 0.1–0.2 g/L of AGEs. The induction process lasted for 48 h, and the skin aging model was induced. Afterwards, 0.1–0.4 g/L of total ketone of Eurasian cyclodextrin was administered for a continuous duration of 6 h. Then, pharmacodynamic testing was conducted, and the experimental results showed that the total ketones of Eurasian spiny flowers can inhibit the specific receptors of glycation end products [125]. This indicates that the total flavonoids of Eurasian Convolvulus can prevent skin aging.
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- Epimedin C: Epimedin C is the major flavonoid from Herba epimedii [126]. HaCat cells were employed to construct a skin aging model in which AGEs were used. The HaCat cells were treated with a concentration of 1000 μg/mL of AGEs to create the skin aging model. Additionally, the drug was administered to the HaCat cells at a concentration ranging from 100 to 300 μM. Pharmacodynamic testing was performed after 24 h of administration. The results showed that Epimedin C can reduce ROS, inhibit the abnormal expression of the MMPs family, inhibit an increase in the apoptotic protein Bax, inhibit an increase in cyclooxygenase Cox-2, and inhibit the expression of IL-6 and IL-8 [127]. This suggests that Epimedin C has an anti-aging effect on the skin.
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- Schisandrin A, Schisandrin B, and Schisandrin C: Schisandrin B has a protective effect against skin tissue oxidative stress induced by solar radiation and can prevent skin photoaging [128]. Using HaCat cells for experiments through 50–200 μM of hydrogen peroxide for modeling, a model was established after 4 h. Concentrations of 100–200 μM of Schisandrin A, Schisandrin B, and Schisandrin C were administered for 12 h. Oxidative damage reactions were tested to determine the cell survival rate and the experimental results showed that Schisandrin A, Schisandrin B, and Schisandrin C had a certain protective effect against oxidative damage [129]. This indicates that Schisandrin A, Schisandrin B, and Schisandrin C have certain anti-aging effects.
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- Cordycepin (3-deoxyadenosine): Cordycepin has anti-inflammatory effects. It was used to create a UVB model of human dermal fibroblasts, lasting for 24 h, which were then administered with cordycepin. The experimental results showed that 50 μM and 100 μM of cordycepin can reduce the expression of MMPs and inhibit the activation of NF-κB to prevent skin photodamage caused by UVB [130]. This indicates that cordycepin has an anti-aging effect on the skin.
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- Astragaloside IV: Astragaloside IV is one of the main active ingredients extracted from Astragalus membranaceus. It has the effect of resisting light aging [131]. Human skin fibroblasts were utilized, specifically by selecting aged skin fibroblasts derived from elderly individuals. These aged skin fibroblasts were then treated with a concentration of 5–20 μg/mL of astragaloside IV and monitored over a duration of 24–120 h. The experimental results showed that the astragaloside IV promoted collagen synthesis in skin cells and reduced the cell apoptosis rate [132]. This indicates that astragaloside IV has a certain anti-aging effect.
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- Ginsenoside Rb1: Ginsenoside Rb1 has various pharmacological effects, including anti-inflammatory, anti-stress, anti-aging effects, etc. [133]. This experiment was conducted using human dermal fibroblasts and hydrogen peroxide (600 μM) for modeling, with a modeling time of 3 h. After 3 h of modeling, Ginsenoside Rb1 (500 μM) was added for 2 h. The results demonstrated that the Ginsenoside Rb1 exhibited a significant resistance to the toxicity of hydrogen peroxide, and embodied a mechanism of action to reduce the ROS value [134,135]. This implies that ginsenoside Rb1 can resist skin aging.
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- Vitamin D3: Vitamin D3 is produced in the skin from 7-dehydrocholesterol [136]. Vitamin D3 and its active metabolites can effectively protect against photodamage, reducing skin aging through multiple mechanisms, including immune regulation and DNA repair [137]. Human epidermal keratinocytes were used for modeling through UVB (50 mJ/cm2), and the cells were pre-treated with active vitamin D3 and L3 hydroxyderivatives for 24 h. By activating Nrf2, which functions in cytoprotection and detoxification, these compounds reversed the UVB-mediated ROS production, thus attenuating photoaging. These compounds also stimulated the expression of antioxidant-response genes, including GR, HO-1, CAT, SOD-1, and SOD-2, as well as the expression of HO-1, CAT, and MnSOD proteins [138]. This indicates that vitamin D3 promises to be a skin photoprotector.
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- Metformin: Metformin can repair DNA damage, clear ROS, and protect cells [139]. Human skin fibroblasts were used for modeling through UVA, and metformin with a drug concentration of 1 mmol/L was used for 72 h of a drug treatment. An analysis of the skin aging-related indicators showed that the positive rate of β-galactosidase staining decreased, the ROS levels decreased, the expression levels of MMP-1 and MMP-3 decreased and the expression levels of SOD1 and SOD2 also increased [140]. This indicates that the degree of skin aging had improved.
4. Discussion
4.1. Clinical Studies on Human Subjects
4.2. Animal Experiments
4.3. Experimental Studies on Cell Cultures
4.4. Skin Anti-Aging Tactics
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
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No. | CAS No. | Compound Category | Classification of Compound Structures | Drug/ Compound | Subjects | Administration | Mechanisms | References |
---|---|---|---|---|---|---|---|---|
Oral administration (dietary) | ||||||||
1 | 24696-26-2 | Natural compounds | Amides | Ceramide | 30 adults aged 20–60 (men and women) | 4 w | Skin barrier↑ | Tsuchiya, 2020 [42]; Tsuchiya, 2021 [43] |
2 | 68-26-8 | Natural compounds | Enols | Retinol | 24 women aged 18–65 with acne, etc. | 6 w | Collagen↑ | Shao, 2017 [44]; Sadick, 2019 [45] |
3 | 9004-61-9 | Natural compounds | Saccharide | Hyaluronic acid | 60 women with aging skin | 12 w | Collagen integrity↑ | Yoshida, 2019 [46]; Michelotti, 2021 [47] |
4 | 472-61-7 | Natural compounds | Terpenes | Astaxanthin | 23 healthy women | 10 w | Oxidation↓, inflammation↓ | Zhou, 2021 [48]; Iwona, 2021 [49]; Ito, 2018 [50] |
5 | 2239-67-0 | Synthetic compounds | Peptides | Gly-Pro-Hyp | 64 women | 12 w | Collagen degradation↓ | Chae, 2023 [51]; Kim, 2018 [52] |
Topical administration or injection | ||||||||
6 | 14024-63-6 | Natural compounds | Aminoketones | AZ | 31 healthy women aged 44 ± 7 | 8 w, applied to face | ROS↓ | Swindell, 2020 [53]; Dhaliwal, 2021 [54] |
7 | 989-51-5 | Natural compounds | Catechols | EGCG | 88 women | 12 w, applied | ROS↓, DNA loss↓ | Tong, 2014 [56]; Lei, 2023 [55] |
8 | 78619-96-2 | Natural compounds | Esters | Vitamin C | 50 women | 4–8 w, applied to face | ROS↓ | Akbari, 2014 [57]; Rattanawiwatpong, 2020 [58] |
9 | 73-31-4 | Natural compounds | Indoles | Melatonin | 22 women with moderate-severe skin aging | 12 w, apply to face | ROS↓ | Bocheva, 2022 [59]; Milani, 2018 [60] |
10 | 99-50-3 | Natural compounds | Phenolic acids | Protocatechuic acid | 22 women | 8 w, applied to face | Oxidation↓, inflammation↓ | Shin, 2020 [62]; Nam, 2018 [61]; |
11 | 10309-37-2 | Natural compounds | Phenols | Nature-based bakuchiol | 60 women with sensitive skin | 4 w, apply to face | Oxidation↓ | Bluemke, 2022 [63]; Draelos, 2020 [64] |
12 | 6155-35-7 | Natural compounds | Saccharide | Rhamnose | 20 healthy women aged 50–68 | 8 w, applied to forearm | AGEs↓ | Péterszegi, 2008 [66]; Robert, 2010 [65]; Pageon, 2019 [67]; |
13 | 41059-79-4 | Natural compounds | Saponins | TA-III | 21 women who had started to develop or had already developed wrinkles | 12 w, applied | Inflammation↓, photoaging↓ | Im, 2020 [70]; Lin, 2020 [68]; Kim, 2019 [69] |
14 | 26811-96-1 | Synthetic compounds | Esters | PLLA | 40 Healthy women | 12 months, injected in the face | Collagen synthesis↑ | Oh, 2023 [71]; Bohnert, 2019 [72] |
15 | 638-26-6 | Synthetic compounds | Fatty acids | 10-HSA | 42 Caucasian women with Fitzpatrick skin types II-III | 8 w, applied to face | Collagen↑ | Rawlings, 2021 [73]; Schütz, 2019 [74] |
16 | 79-14-1 | Synthetic compounds | Hydroxyl acids | GA | 262 women aged 30–60 with photoaging skin | 2 w, applied to face | Inflammation↓, photoaging↓ | Tang, 2019 [75]; Santos-Caetano, 2020 [76] |
No. | CAS No. | Compound Category | Classification of Compound Structures | Drugs/ Component | Animals | Modeling Methods | Modeling Time | Administration | Mechanisms | Reference |
---|---|---|---|---|---|---|---|---|---|---|
Oral administration (dietary) | ||||||||||
1 | 28448-85-3 | Natural compounds | Flavonoids | Bavachalcone | WT and TET3+/− C57BL/6J mice | Intraperitoneal injection of paraquat 10 mg/kg | from w 6 to w 40 | 20 mg/kg by gavage every day | MDA↓, SOD↑, CAT↑, Hyp↑ | Meng, 2019 [77]; Yuan, 2019 [79] |
2 | Natural compounds | Polyphenols | BPP | SD Rat | Subcutaneous injection of d-galactose 300 mg/kg | 7 w | 120 mg/kg by gavage for 7 w | MMP-1↓, collagen↑ | Kai, 2010 [80]; Yu, 2020 [81] | |
3 | 458-37-7 | Natural compounds | Polyphenols | Curcumin | BALB/c-nu/nu mice | Subcutaneous injection of d-galactose 125 mg/kg | 3 w | 80 mg/kg by gavage for 3 w | MDA↓, SOD↑, Hyp↑ | Ben Yehuda Greenwald, 2017 [82]; Heng, 2010 [83]; Hui, 2016 [84]; Min, 2023 [85] |
4 | 4852-22-6 | Natural compounds | Polyphenols | Procyanidins | Kunming female mice | 5% D-galactose 10 mL/kg was injected subcutaneously every day, and radiation was carried out the next day | 40 d | 50–100 mg/kg procyanidins orally administered for 30 d | MDA↓, SOD↑, GSH-Px↑, Hyp↑, | Weng, 2022 [86]; Juan, 2018 [87]; Fei, 2020 [88]; Rong, 2022 [89] |
5 | 501-36-0 | Natural compounds | Polyphenols | Resveratrol | Adult female Wistar rats | Excision of bilateral ovaries | 31 d | Gavage 10, 30, and 60 mg/kg for 31 d | MDA↓, SOD↑, SIRT1 protein↑, Hyp↑ | Leis, 2022 [90]; Dong,2015 [91]; Hecker, 2022 [92] |
6 | 6640-24-0 | Natural compounds | Polysaccharides | CPP | Kunming female Mice | Subcutaneous injection of 5% d-galactose solution 1 g/kg | 42 d | 50–150 mg/kg gavage for 32 days | MDA↓ | Fude, 2023 [93]; Nong, 2014 [94] |
7 | 107310-89-0 | Natural compounds | Polysaccharides | LBP | Kunming female Mice | Subcutaneous injection of d-galactose 1000 mg/kg/d | 42 d | 5–20 mg kg−1 per day by gavage for 42 days | MDA↓, SOD↑, GSH-Px↑, Hyp↑ | Zhu, 2022 [95]; Neves, 2021 [96]; Xia, 2015 [97]; Lei, 2023 [98] |
8 | Natural compounds | Polysaccharides | SMMP | Kunming female Mice | Subcutaneous injection of d-galactose 10 mL/kg/d +40 min, 5% UVB per day | 40 d | Gavage 4 g/kg/d, starting from day 11 to day40 | MDA↓, SOD↑, GSH-Px↑, Hyp↑ | Nan, 2019 [99]; Hong, 2020 [100] | |
9 | 72909-34-3 | Natural compounds | Quinones | PQQ | Bmi-1-knock out BKO mice | Knock out Bmi-1 gene | PQQ 4 mg per kilogram of feed for 4 w | Oxygen free radicals↓, collagen↑ | Li, 2022 [101]; Yuan, 2017 [102] | |
Topical administration or injection | ||||||||||
10 | 78-70-6 | Natural compounds | Monoterpenes | l-linalool | Female ICR mice | Subcutaneous injection of d-galactose 1.5 mg/g/d | 30 d | Applied 5.0% to dorsal skin tissue for 30 d | Oxygen free radicals↓, MDA↓, SOD↑, Hyp↑ | Keng, 2021 [104] |
11 | 1094-61-7 | Natural compounds | Nucleosides | NMN | ICR mice | 12 h of UVB irradiation light/dark cycle per day | 1 w | 300 mg/kg by intraperitoneal injection for 3 w | SOD↑, TNF- α↓, IL-1 β↓, IL-6↓ | Feng, 2022 [105]; Zhou, 2021 [106] |
12 | 117-39-5 | Natural compounds | Polyphenols | Quercetin | Male Kunming mice | Subcutaneous injection of d-galactose 200 mg/kg/d | 8 w | Subcutaneous injection of 10–20 mg/kg/day for 8 w | SOD↑, T-AOC↑, GSH-Px↑, collagen↑ | Shin, 2019 [107]; Xiao, 2022 [108] |
13 | 10191-41-0 | Natural compounds | Polyphenols | Vitamin E | Pig skin homogenate from Hainan breeding pigs | Using 20–100μL of Vitamin E (≥98%) and avoiding light reaction for 1 h | SOD↑, CAT↑ | Nachbar, 1995 [118]; Lei, 2013 [109] | ||
14 | 9012-76-4 | Natural compounds | Polysaccharides | Chitosan | SD Rat | Daily application of chitosan (M = 106) 1% solution for 30 days, applied to dorsal skin | Hyp↑, collagen↑ | Kong, 2018 [110]; Xing, 2022 [111]; Chun, 2018 [112] | ||
15 | 102607-24-9 | Natural compounds | Polysaccharides | GLP | Kunming Mice | Subcutaneous injection of d-galactose 1000 mg/kg/d | 6 w | Applied 0.5% ganoderma lucidum polysaccharide to skin tissue for 42 days | DPPH↓, MDA↓, SOD↑, Hyp↑ | Hu, 2019 [113]; Ye, 2020 [114] |
16 | Natural compounds | Polysaccharides | WGP | Mice | Subcutaneous injection of d-galactose 500 mg/kg/d | 6 w | 5 mg/mL of winter melon polysaccharide was applied to dorsal skin tissue at a rate of 2 m per day for 6 w | Oxygen free radicals↓, MDA↓, SOD↑, CAT↑, tyrosinase↓ | Yibei, 2020 [115]; Xiao-yan, 2018 [116]; | |
17 | 79-14-1 | Synthetic compounds | Hydroxy acids | Hydroxyacetic acid | Kunming mice | Subcutaneous injection of d-galactose 1 mg/g/d | 12 w | Applied 50% and 70% hydroxyacetic acid once every two weeks, applied to dorsal skin | Collagen↑, elastic fibers↑ | Tang, 2019 [75]; Xiao, 2019 [117] |
No. | CAS No. | Compound Category | Classification of Compound Structures | Drugs/ Compounds | Cells | Modeling Methods | Modeling Time | Treatment | Mechanisms | References |
---|---|---|---|---|---|---|---|---|---|---|
1 | 29946-61-0 | Natural compounds | Alkaloids | GX-50 | Primary human skin fibroblasts | Hydrogen peroxide, (50 μM) | Once every two days, a total of 4 times | 100 μM once every two days, a total of 4 times | ROS↓, MDA↓, the positive rate of β-Galactosidase↓ | Ping, 2015 [119]; Shi, 2016 [141]; Xue-feng, 2013 [120] |
2 | 1124-11-4 | Natural compounds | Alkaloids | Ligustrazine | Human skin fibroblasts | UVA (10 J /d) | 5 d | Ligustrazine hydrochloride injection 2 mL: 40 mg for 5 days | ROS↓, MMP-1↓, MMP-3↓, p53↓, the positive rate of β-Galactosidase↓ | Liu, 2022 [121]; Ling, 2015 [122] |
3 | 104594-70-9 | Natural compounds | Catechols | CAPE | Human Dermal Fibroblasts-adult | UVA94.5% + UVB5% | 48 h | 5 uM for 48 h | MMP-1↓, collagen↑ | Shin, 2019 [124] |
4 | Natural compounds | Flavonoids | Total flavonoids of Eurasian Convolvulus | Mouse skin fibroblasts | AGEs (0.1–0.2 g/L) | 48 h | 0.1 g/L–0.4 g/L Continuous action for 6 h | AGEs↓ | Lu, 2018 [125] | |
5 | 110642-44-9 | Natural compounds | Flavonoids | Epimedin C | HaCat cells | AGEs (1000 μg/mL) | 1 h | 100–300 μM for 24 h | ROS↓, MMPs↓, Cox-2↓, IL-6↓, IL-8↓ | Bowen, 2019 [127] |
6 | 61281-38-7, 61281-37-6, 61301-33-5 | Natural compounds | Lignans | Schisandrin A, Schisandrin B, and Schisandrin C | HaCat cells | Hydrogen peroxide (50, 100, and 200 μM) | 4 h | 100 and 200 μM Schisandrin A, Schisandrin B, and Schisandrin C for 12 h | Oxidative damage↓ | Lam, 2011 [128]; Wei, 2013 [129] |
7 | 73-03-0 | Natural compounds | Nucleosides | Cordycepin | Dermal fibroblasts | UVB | 24 h | 50–100μM for 24 h | MMPs↓ | Lee, 2009 [130] |
8 | 84687-43-4 | Natural compounds | Saponins | Astragaloside IV | Aging human skin fibroblasts | 5–20μg/mL administration monitoring within 24–120 h | Collagen↑ | Chen, 2015 [131]; Xi, 2006 [132] | ||
9 | 22427-39-0 | Natural compounds | Saponins | Ginsenoside Rb1 | Human dermal fibroblasts | 600μM Hydrogen peroxide | 3 h | 500 μM for 2 h | ROS↓ | Oh, 2015 [133]; Zhiwen, [134]; LIU Chun Xian, 2022 [135] |
10 | 67-97-0 | Natural compounds | Steroids | Vitamin D3 | Human epidermal keratinocytes | UVB (50 mJ/cm2) | 24 h | 100 nM for 24 h | ROS↓, SOD↑ | Bocheva, 2021 [137]; Chaiprasongsuk, 2019 [138] |
11 | 657-24-9 | Synthetic compounds | Biguanides | Metformin | Human skin fibroblasts | UVA 5 J/cm2 for consecutive 3 days | 24 h | 1 mmol/L for 72 h | ROS↓, SOD↑, MMP-1↓, MMP-3↓, the positive rate of β-Galactosidase↓ | Chen, 2022 [139]; Yi, 2017 [140] |
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He, X.; Wan, F.; Su, W.; Xie, W. Research Progress on Skin Aging and Active Ingredients. Molecules 2023, 28, 5556. https://doi.org/10.3390/molecules28145556
He X, Wan F, Su W, Xie W. Research Progress on Skin Aging and Active Ingredients. Molecules. 2023; 28(14):5556. https://doi.org/10.3390/molecules28145556
Chicago/Turabian StyleHe, Xin, Fang Wan, Wenhui Su, and Weidong Xie. 2023. "Research Progress on Skin Aging and Active Ingredients" Molecules 28, no. 14: 5556. https://doi.org/10.3390/molecules28145556