| Sunlight is an important environmental factor, which is further divided into various electromagnetic radiations e.g., ultraviolet(UV) light that spanned 100-400 nm of solar spectrum. Ultraviolet radiations can be classified into further sub-classes such as UV light with wavelengths of 100-280 nm is the UVC, which being absorbed by the upper stratospheric layers and in general does not enter into the biosphere. While wavelength between 280-320 nm called UVB, where the longer wavelength 320-400 nm is UVA. There exit inverse relationship with the energy and wavelength of UVs i.e., longer the wavelength is less the energy and vice versa. Our skin gets exposed to UV radiations which cause numerous skin conditions particularly erythema, sunburn, photo-aging, photodermatosis and carcinogenesis. Contemporary, UV is also very benefitto our skin: it synthesizes activated pre-form of vitamin D3, immunomodulatory responses, rise in the blood circulation, promote healing of wounds, lessen pains and pigmentation of the skin.Chronic exposures of solar UVA(320-400 nm) to human skin may aid accumulate excessive and persistent reactive species hence imbalance redox status of the cells, liberated free heme from microsomal protein bodies, degrade ferritin to raise labile iron, which may initiate proinflammatory factors. Photoaging is a term to described UVs driven premature aging of the tissues and skin, increase in the wrinkles formation, pigmentation, and leathery texture of the skin. UVA radiation exposures broken down collagen and alter the composition of the collagenous tissues in extracellular matrixes(ECM). Both extrinsic and intrinsic factors lead the activation or expression of MMPs genes. Extrinsic factors such as UVs(UVA, UVB, UVC), chronic sun exposure, heat, air pollution, drier or hot environment, smoke etc., while among the intrinsic factors are different chemokines, cytokines(ILs) and inflammatory factors(TNF?, TGF?). Of the various intrinsic factors, externally produced TGF-? which after entry into the cells gets activated by proteases may target Smads, a key regulator of MMPs and ECM expressions. Some reports showed that antioxidants may modulate these factors and therefore protect against UVA-mediated damage. In this study, we investigated AKBA, Burberine, and eriodictyol and their protective effects on skin cells against UVA damage.ResultsIncreasing UVA irradiation change the normal cell morphology to somewhat rounded to oval shaped cells, and decreases the cell viability 24 h post irradiation in HaCaT cells. Pre-treatment with ER(20 ?M) and AKBA(1.5 ?M), while post UVA irradiation treatment with BBR(5.0 ?M) reduced the cell viability loss incurred by UVA.HaCaT cells shown prompt response to the UVA irradiation in the form of increased levels of reactive oxygen species(ROS) and hence the redox balance of the cells disturbed. Compared to control, 150 and 300 KJ/m2 UVA doses showed 2.9-fold and 3.5-fold increased the ROS in a dose dependent way. For UVA 150KJ/m2 ER 20 ?M decreased ROS from 2.91 to 2.49, while 300 KJ/m2 ER 20 ?M significantly decreased the ROS from 3.5 to 2.70. While, BBR 5.0 and 10 ?M significantly decreased ROS level from 3.13-fold to 2.26-fold and 2.22-fold with UVA 150 KJ/m2. While at 300 KJ/m2 the ROS increased to 3.6-fold, which was significantly reduced to 2.33-fold and 2.17-fold by 5.0 ?M and 10.0 ?M BBR, respectively.UVA potentially damage the cellular membranes to release LDH. Following UVA, the LDH release was increased in HaCaT cells. The pre-treatment with ER, and post UVA irradiation treatment of BBR, significantly decreased the LDH release in a concentration manner. The overall maximum decrease in LDH release was seen at 40 ?M of ER and 20 ?M of BBR treatment, significantly reduced LDH leakage in HaCaT and FEK-4 fibroblast cells.The UVA irradiation lowered SOD activity to almost 60%, while ER pretreatment(5, 10, 20, 40 ?M) significantly increased the depletion in SOD to almost basal level at 40 ?M concentration with almost 35% of recovery. In the BBR treated cells, the SOD depletion was recovered from 60% to 99% with 20 ?M BBR. MMP-1(collagenase-1)expression was significantly reduced by ER and BBR treatments to HaCaT cells as quantified by ELISA. ER(20?M) reduced almost 25% of MMP-1 secretion, while BBR(10 ?M) gave only 15% reduction in MMP-1 secretion, when compared to the UVA irradiated HaCaT cells.ER and AKBA suppressed the expression of various inflammatory cytokines. Pretreatment of ER(20 ?M) for 12 h, significantly reduced the UVA-induced expression of IL-1? 1.8-fold to 0.8-fold, for IL-6 from 2.4-fold to 1.4-fold, TNF? from 1.75-fold to 1.3-fold, TGF? 3.30-fold to 0.9-fold, COX-2 from 1.6-fold to 1.1-fold and NF?B 7-fold downs to 2.5-fold. UVA(150 KJ/m2) may activated the expression of MMP-1(20%) in human skin HaCaT cells, while pre-treatment with eriodictyol lessen and reduce this expression in a concentration dependent way and reduced it to basal level by 20 ?M ER, while BBR(10 ?M) highly significantly decreased the expression of MMP-1 genes. For COL-I,-III activity in ER and BBR treated cells, both the drugs recovers the UVA decreased collagenase activity and level to basal in a concentration manner. TIMP-1 in ER pre-treated HaCaT cells and in BBR treated cells was increased with increasing concentration.UVA irradiation immediately triggers the phsophorylation of these ERK, JNK, p38 and NF?B(30 minutes), but the pretreatment of ER 20 ?M for 12 h, suppressed the phosphorylation of p-ERK1/2 to almost half that of the UVA. BBR(5.0 ?M) also suppresses the phosphorylation of ERK, JNK, p38 and NF?B. BBR(5.0 ?M) has non-significant effect on the phosphorylation of p-ERK while p-JNK was reduced to 7% compared to its UVA treated group. Effect of BBR treatment on p-38 was almost 50-60%, and phosphorylation of NF?B about 45% reduced in the co-treatment of BBR+UVA.SummaryBoth ER and BBR reduce UVA-induced MMP-1 up-regulation and hence pose the photoprotective effect in HaCaT cells,they reduce the oxidative stress generated by UVA irradiation in HaCaT cells in a dose dependent manner. ER down-regulated UVA activated c JUN/c-FOS activity in a dose dependent manner. Both ameliorated damaging effects of UVA, and rescued cell death hence can be potential candidates for the skin care products, though further indepth studies involving animal models are still needed. AKBA Lower UVA induced oxidative stress in skin cells, evoke cellular defense system(NRF2/ARE Pathway) and provide cytoprotection in HaCaT cells. Its Hydrophobic in nature, hence less bioavailability, strong lipophilic in nature. We combined UVA light and Zn O loaded AKBA(AKBA@Zn O), and gradually released the drug and simultaneously pose skin protection and sun blocking upon UVA exposure on the skin cells. It maximize AKBA molecule delivery at targeted sight, because the AKBA is hydrophobic in nature. In both HaCaT and FEK-4 fibroblast cells it provide, anti-inflammatory effects by reducing IL-1?, IL-6, NF?B, TNF? and TGFb. Furthermore, AKBA reduced UVA induced cell viability loss. AKBA@Zn O NP, could be a useful therapeutics against UVA related skin condition. AKBA@Zn O+UVA, co-treatment for sun related diseases i.e., provide protection and therapy at the same time are crucial and desirable. Future prospects includes all three chemicals ER, BBR, AKBA have a potential to be used in skin care products. Indepth investigations for clinical applications of these drugs are essential. We still working for further indepth studies. ER, BBR and AKBA shown anti-photoaging and photodamage potential. |
PDF Full Text Request