## 5 Antioxidants from Natural Products as Alternative Treatment
### Resveratrol (RSV)  
Resveratrol (RSV), a natural polyphenol found in red grapes and berries, is recognized for its potent antioxidant properties. Its ability to scavenge free radicals and reduce inflammation positions it as a potential therapeutic agent in diseases like psoriasis, where oxidative stress and inflammation play significant roles [89; 90]. Preclinical studies have investigated the efficacy of RSV in psoriasis treatment, yielding promising results that suggest its potential as a novel approach to managing this challenging condition. Preclinical trials exploring RSV's use in psoriasis treatment have reported reductions in disease severity in mice treated with RSV-based formulations. RSV has demonstrated modulation of various signaling pathways involved in inflammation and immune responses, further contributing to its anti-posoriatic effects. For instance, the development of resveratrol-loaded polymeric micelles (PMs) using a Quality by Design (QbD) approach has shown significant promise in addressing the challenge of poor permeability in psoriatic skin [91]. In an IMQ-induced psoriatic-like plaque model in mice, the optimized PM converted into a gel (PMG) demonstrated superior efficacy compared to conventional gel (CG), with lower levels of hyperkeratosis, serum cytokines, and PASI scores [91]. This suggests that the PMG has potential for improved topical delivery and therapeutic advantages in the treatment of plaque psoriasis.  
RSV has also shown the ability to inhibit the proliferation of keratinocytes, the predominant cell type in psoriatic epidermis. By regulating keratinocyte proliferation, RSV helps restore the balance of cell turnover in the skin, leading to improvements in psoriatic lesions. Studies have demonstrated RSV's effects on keratinocyte apoptosis and the modulation of signaling pathways involved in psoriasis pathogenesis, along with enhancing antioxidant activity. For instance, RSV treatment raised Sirt1 expression in keratinocytes, leading to inhibition of Akt phosphorylation and apoptosis of human HaCaT cells [92]. A study also exhibits that RSV has antioxidant and anti-proliferative properties on normal human epidermal keratinocytes (NHEKs) by reducing the expression of aquaporin 3 (AQP3), which is excessively produced in hyperplastic skin diseases such as psoriasis [93]. Inhibition of NHEK proliferation by RSV is facilitated by the SIRT1/ARNT/ERK pathway, in which increased SIRT1 expression results in lower ERK phosphorylation and reduced AQP3 expression [93]. The results indicate that RSV has potential as a therapeutic agent for controlling psoriasis by intervening in pathways that control the growth of skin cells.  
In addition, a study conducted by [PERSON] et al. observed the effects of RSV on imqiumod-induced psoriasis-like skin inflammation in mice. RSV modulated IL-17 signaling pathways and mRNA levels of IL-17A and IL-19, suggesting its potential as a treatment for psoriasis [94]. It also significantly decreased the severity of inflammation by decreasing the thickness of the mice's skin [94]. Despite promising evidence, further research is needed to optimize the dosage, formulation, and long-term safety of RSV in psoriasis treatment. Moreover, extensive clinical trials are warranted to validate its efficacy and assess its potential benefits for different psoriasis subtypes and patient populations. In conclusion, RSV emerges as a natural antioxidant with anti-posoriatic properties, offering potential avenues for further exploration in the management of psoriasis.