Structure characterization and protective effect against UVB irradiation of polysaccharides isolated from the plateau plant Gentiana dahurica Fisch.

Gentiana dahurica Fisch. (G. dahurica) is one of the legitimate sources of Qinjiao in Traditional Chinese Medicine (TCM) and grows on high-altitude plateaus. Plants develop unique biochemical accumulations to resist plateau conditions, especially the strong UV irradiation. Thus, this study aimed to investigate the polysaccharide of G. dahurica (GDP), its structure and its activity against UVB irradiation. Four GDPs were isolated and two of them were subjected to structural elucidation. The results suggested that GDP-1 has 53.5 % Ara and 30.8 % GalA as its main monosaccharides, with a molecular weight (Mw) of 23 kDa; the GDP-2 has 33.9 % Ara and 48.5 % GalA, with a Mw of 82 kDa. Methylation and NMR spectroscopy analysis revealed that GDP-1 contains →5)-α-Araf-(1 â†’ 5)-α-Araf-(1 â†’ 3,5)-α-Araf-(1 â†’ 3,4)-α-GalpA-(6-OMe)-(1→ as the main chain, the branches of GalA (with esterification), and the terminal Ara; the GDP-2 contains →4)-α-GalpA-(1 â†’ 4)-α-GalpA-(6-OMe)-(1 â†’ 5)-α-Araf-(1 â†’ 3,5)-α-Araf-(1→ as the main chain, the branches of →5)-α-Araf-(1-5)-α-Araf, and the terminal GalA. Both GDP-1 and GDP-2 exhibited concentration-dependent antioxidant activity against DPPH, ABTS and hydroxyl radicals. Moreover, GDPs significantly attenuated the decreases in viability and proliferation of HaCaT cells after UVB irradiation. They can scavenge reactive oxygen species (ROS) and improve the activities of endogenous antioxidant enzymes, including superoxide dismutase (SOD) and glutathione peroxidase (GSH). The potential mechanism explored by flow cytometry assays of cell apoptosis and cell cycle distribution suggested that GDPs exert protective effects against UVB irradiation by reducing ROS and attenuating S phase cell arrest. In brief, the GDP-1 and GDP-2 are α-1,3- and α-1,4- arabinogalacturonan, respectively. The high content of Ara could be attributed to biochemical accumulation in resisting to the plateau environment and to prevent UVB irradiation-related damage in cells. These findings provide insight into authentic medicinal herbs and the development of GDPs in the modern pharmaceutical and cosmetics industry.

Disrupted gut microecology after high-dose 131I therapy and radioprotective effects of arachidonic acid supplementation.

BACKGROUND: Despite the potential radiotoxicity in differentiated thyroid cancer (DTC) patients with high-dose 131I therapy, the alterations and regulatory mechanisms dependent on intestinal microecology remain poorly understood. We aimed to identify the characteristics of the gut microbiota and metabolites in DTC patients suffering from high-dose 131I therapy and explore the radioprotective mechanisms underlying arachidonic acid (ARA) treatment. METHODS: A total of 102 patients with DTC were recruited, with fecal samples collected before and after 131I therapy for microbiome and untargeted and targeted metabolomic analyses. Mice were exposed to total body irradiation with ARA replenishment and antibiotic pretreatment and were subjected to metagenomic, metabolomic, and proteomic analyses. RESULTS: 131I therapy significantly changed the structure of gut microbiota and metabolite composition in patients with DTC. Lachnospiraceae were the most dominant bacteria after 131I treatment, and metabolites with decreased levels and pathways related to ARA and linoleic acid were observed. In an irradiation mouse model, ARA supplementation not only improved quality of life and recovered hematopoietic and gastrointestinal systems but also ameliorated oxidative stress and inflammation and preserved enteric microecology composition. Additionally, antibiotic intervention eliminated the radioprotective effects of ARA. Proteomic analysis and ursolic acid pretreatment showed that ARA therapy greatly influenced intestinal lipid metabolism in mice subjected to irradiation by upregulating the expression of hydroxy-3-methylglutaryl-coenzyme A synthase 1. CONCLUSION: These findings highlight that ARA, as a key metabolite, substantially contributes to radioprotection. Our study provides novel insights into the pivotal role that the microbiota-metabolite axis plays in radionuclide protection and offers effective biological targets for treating radiation-induced adverse effects.

Enhancing radioprotection: A chitosan-based chelating polymer is a versatile radioprotective agent for prophylactic and therapeutic interventions against radionuclide contamination.

To mitigate the risk of radioactive isotope dissemination, the development of preventative and curative measures is of particular interest. For mass treatment, the developed solution must be easily administered, preferably orally, with effective, nontoxic decorporating properties against a wide range of radioactive isotopes. Currently, most orally administered chelation therapy products are quickly absorbed into the blood circulation, where chelation of the radioactive isotope is a race against time due to the short circulation half-life of the therapeutic. This report presents an alternative therapeutic approach by using a functionalized chitosan (chitosan@DOTAGA) with chelating properties that remains within the gastrointestinal tract and is eliminated in feces, that can protect against ingested radioactive isotopes. The polymer shows important in vitro chelation properties towards different metallic cations of importance, including (Cs(I), Ir(III), Th(IV), Tl(I), Sr(II), U(VI) and Co(II)), at different pH (from 1 to 7) representing the different environments in the gastrointestinal tract. An in vivo proof of concept is presented on a rodent model of uranium contamination following an oral administration of Chitosan@DOTAGA. The polymer partially prevents the accumulation of uranium within the kidneys (providing a protective effect) and completely prevents its uptake by the spleen.

Anti-radiation effect of MRN-100: a hydro-ferrate fluid, in vivo.

Ionizing radiation (IR) severely harms many organs, especially the hematopoietic tissue, mandating the development of protective nutraceuticals. MRN-100, a hydro-ferrate fluid, has been shown to protect γ-radiated fish against hematopoietic tissue damage and lethality. The current study aimed to examine MRN-100's protective effect against irradiated mice and explore the mechanisms underlying its effect. Mice received a single acute, sub-lethal, 5 Gy, whole body dose of X-ray IR. MRN-100 treatment was administered daily for 2-weeks pre-irradiation until 1-week post-irradiation. Spleen and blood were analysed for oxidative stress, hematological, histological and biochemical parameters. Radiation exposure markedly decreased complete blood count (CBC) parameters including hemoglobin, hematocrit, red blood cells, platelets, white blood cells and lymphocytes, and significantly increased neutrophils. In contrast, MRN-100 supplementation to irradiated mice ameliorated all CBC parameters and protected against DNA damage in both splenic cells and serum. It also had an antioxidant effect, increasing the levels of glutathione, superoxide dismutase, catalase and total antioxidant capacity, which were otherwise decreased by irradiation. MRN-100 intake reduced the oxidative stress biomarker levels of nitric oxide, protein carbonyl, malondialdehyde, reactive oxygen species and 8-hydroxydeoxyguanosine, a marker specific to DNA damage. Furthermore, MRN-100 enhanced serum iron and reversed the radiation-induced elevations of liver enzymes. Finally, MRN-100 protected splenic tissue from irradiation as observed by histology. We conclude that MRN-100 consumption may protect against oxidative stress generated by radiation exposure, suggesting that it may be employed as an adjuvant treatment to prevent radiation's severe damage to important organs.

Development of radiation countermeasure agents for acute radiation syndromes.

The risk of internal and external exposure to ionizing radiation (IR) has increased alongside the development and implementation of nuclear technology. Therefore, serious security issues have emerged globally, and there has been an increase in the number of studies focusing on radiological prevention and medical countermeasures. Radioprotective drugs are particularly important components of emergency medical preparedness strategies for the clinical management of IR-induced injuries. However, a few drugs have been approved to date to treat such injuries, and the related mechanisms are not entirely understood. Thus, the aim of the present review was to provide a brief overview of the World Health Organization's updated list of essential medicines for 2023 for the proper management of national stockpiles and the treatment of radiological emergencies. This review also discusses the types of radiation-induced health injuries and the related mechanisms, as well as the development of various radioprotective agents, including Chinese herbal medicines, for which significant survival benefits have been demonstrated in animal models of acute radiation syndrome.

Orychophragine D:A new 2-piperazinone fused 5-azacytosine type alkaloid with radioprotective activity from the seeds of Orychophragmus violaceus.

A new alkaloid, Orychophragine D (1), together with three known alkaloids, were isolated from the seeds of Orychophragmus violaceus. Orychophragine D represented the first example of 2-piperazinone fused 5-azacytosine skeleton. Their structures and absolute configurations were determined by spectroscopic analyses and X-ray crystallography. Compared to Ex-RAD, compound 1 exhibited a significant radioprotective activity on cell survival of irradiated HUVEC. In vivo experiments showed that 1 not only remarkably enhanced the survival of irradiated mice in 30 days, but also significantly promoted the recovery of the blood system of irradiated mice. These results suggested that 1 was valuable for further research as promising radioprotectors.

A Review of Radiation-Induced Alterations of Multi-Omic Profiles, Radiation Injury Biomarkers, and Countermeasures.

Increasing utilization of nuclear power enhances the risks associated with industrial accidents, occupational hazards, and the threat of nuclear terrorism. Exposure to ionizing radiation interferes with genomic stability and gene expression resulting in the disruption of normal metabolic processes in cells and organs by inducing complex biological responses. Exposure to high-dose radiation causes acute radiation syndrome, which leads to hematopoietic, gastrointestinal, cerebrovascular, and many other organ-specific injuries. Altered genomic variations, gene expression, metabolite concentrations, and microbiota profiles in blood plasma or tissue samples reflect the whole-body radiation injuries. Hence, multi-omic profiles obtained from high-resolution omics platforms offer a holistic approach for identifying reliable biomarkers to predict the radiation injury of organs and tissues resulting from radiation exposures. In this review, we performed a literature search to systematically catalog the radiation-induced alterations from multi-omic studies and radiation countermeasures. We covered radiation-induced changes in the genomic, transcriptomic, proteomic, metabolomic, lipidomic, and microbiome profiles. Furthermore, we have covered promising multi-omic biomarkers, FDA-approved countermeasure drugs, and other radiation countermeasures that include radioprotectors and radiomitigators. This review presents an overview of radiation-induced alterations of multi-omics profiles and biomarkers, and associated radiation countermeasures.

Radioprotective effect of mistletoe extract on intestinal toxicity: in vivo study using adult zebrafish.

PURPOSE: The intestine is a dose-limiting organ in the treatment of intra-abdominal cancer. We previously reported that the extract of mistletoe parasites on Quercus had a more potent radioprotective effect than amifostine in reducing the developmental toxicities of zebrafish embryos. In this study, radioprotection against intestinal toxicity was investigated in adult zebrafish. METHODS: Wild-type adult AB zebrafish were exposed to 45-50 Gy of photon beam irradiation and/or treated with mistletoe extract orally 1 h before. The main endpoints of the study were survival and degree of deformation of the intestinal villi. RESULTS: The median follow-up period was 10 d post-irradiation (range: 7-11 d). A total of 105 zebrafish were used, including 42 in the radiation alone, 42 in the radiation and mistletoe arms, and 21 control subjects (mistletoe alone, mock-irradiated arm). The rate of both significant deformity and death was 53% in the radiation-alone arm, whereas the corresponding rate was 30% in the radiation and mistletoe arms. Significant deformity-free survival rates at 10 d post-irradiation in the radiation alone, and radiation and mistletoe arms were 44.7% (95% confidence interval [CI]:20-54.3) and 68.4% (95% CI:53.8-86.8), respectively (p=.046). The radiation and mistletoe arms showed decreased expression of two of three inflammatory genes (IL-1ß and IL-6) compared to the radiation alone group (p<.05). CONCLUSION: The radioprotective effect against intestinal toxicity was successfully shown in an adult zebrafish model. This result suggests the possibility of clinical use of mistletoe extract for the treatment of abdominal cancers.

The effects of medical linear accelerator X-rays on human peripheral blood lymphocytes in the presence of glucosamine.

Glucosamine is widely prescribed as a dietary supplement used to treat arthritis. In this study, the radioprotective ability of glucosamine was evaluated against radiation-induced genotoxicity and cytotoxicity in human peripheral blood lymphocytes. Blood samples were collected from five healthy male donors and were divided into four groups. Isolated lymphocytes and blood samples were treated with 10 µM of glucosamine for 2 h before exposure to 2 Gy radiation. The radioprotective potential of glucosamine was assessed by micronucleus assay, reactive oxygen species (ROS) level analysis, and flow cytometry. Irradiation significantly increased the micronuclei frequency as compared to the control group. Contrary to that pretreatment with glucosamine before irradiation significantly reduced the frequency of micronuclei. Furthermore, pretreatment with glucosamine significantly prevented the percentage of apoptotic lymphocytes. Also, glucosamine pretreatment significantly reduced the production of ROS in irradiated lymphocytes. This study shows glucosamine to be a potent radioprotector against radiation that induces DNA damage and apoptosis in human lymphocytes. Several additional in vivo and in vitro studies are needed before glucosamine can be considered as a radioprotective candidate in patients undergoing radiation therapy.

Phytochemicals: A potential next generation agent for radioprotection.

BACKGROUND: Radiation hazards are accountable for extensive damage in the biological system and acts as a public health burden. Owing to the rapid increasing in radiation technology, both Ionizing radiation (IR) from natural and man made source poses detrimental outcome to public health. IR releases free radicals which induces oxidative stress and deleterious biological damage by modulating radiation induced signalling intermediates. The efficacy of existing therapeutic approach and treatment strategy are limited owing to their toxicity and associated side effects. Indian system of traditional medicine is enriched with prospective phytochemicals with potential radioprotection ability. PURPOSE: The present review elucidated and summarized the potential role of plant derived novel chemical compound with prospective radioprotective potential. METHOD: So far as the traditional system of Indian medicine is concerned, plant kingdom is enriched with potential bioactive molecules with diverse pharmacological activities. We reviewed several compounds mostly secondary metabolites from plant origin using various search engines. RESULTS: Both compounds from land plants and marine source exhibited antioxidant antiinflammatory, free radical scavenging ability. These compounds have tremendous potential in fine-tuning of several signalling intermediates, which are actively participated in the progression and development of a pathological condition associated with radiation stress. CONCLUSION: Development and explore of an operational radioprotective agent from originated from plant source that can be used as a novel molecular tool to eliminate the widespread damage caused by space exploration, ionizing radiation, nuclear war and radiotherapy has been significantly appreciated. Through extensive literature search we highlighted several compounds from both land plant and marine origin can be implemented for a better therapeutic potential against radiation induced injury. Furthermore, extensive clinical trials must be carried out in near future for better therapeutic modality and clinical efficacy.

Radiomitigation by Melatonin in C57BL/6 Mice: Possible Implications as Adjuvant in Radiotherapy and Chemotherapy.

BACKGROUND/AIM: Melatonin (N-acetyl-5-methoxytryptamine), a chief secretory molecule of the pineal gland, has multiple properties, and numerous clinical investigations regarding its actions are in progress. This study investigated the radiomitigative role of melatonin in C57BL/6 mice. MATERIALS AND METHODS: Melatonin (100 mg/kg) was orally administered once daily starting at 1 h on day 1 and subsequently every 24 h until day 7 after whole-body irradiation (WBI) and survival was monitored for 30 days. The bone marrow, spleen, and intestine were studied to evaluate the mitigative potential of melatonin after radiation-induced damage. RESULTS: Melatonin significantly improved the survival upto 60% and 90% after 9 Gy (lethal) and 7.5 Gy (sub-lethal) WBI, respectively. Melatonin alleviated WBI-induced myelosuppression and pancytopenia, and increased white blood cell, red blood cell, platelet, and lymphocyte (CD4+ and CD8+) counts in peripheral blood. Bone marrow and spleen cellularity were restored through enhanced haematopoiesis. Melatonin ameliorated the damage in the small intestine, and promoted recovery of villi length, crypts number, and goblet cell count. CONCLUSION: Melatonin mitigates the radiation-induced injury in the gastrointestinal and haematopoietic systems. The observed radiomitigative properties of melatonin can also be useful in the context of adjuvant therapy for cancer and radiotherapy.

Reactive oxygen species-responsive nanodrug of natural crocin-i with prolonged circulation for effective radioprotection.

With the progress of nuclear technology including radiotherapy and radiodiagnosis, radiation has been widely used in many fields as a powerful diagnostic and therapeutic tool in the medical area. Unfortunately, acute radiation disease will occur if the human body is accidentally exposed to a large dosage of ionizing radiation. However, clinical radioprotective agents are being challenged by the short half-life and several side effects. In this work, a reactive oxygen species-responsive nanodrug is developed for efficient radioprotection. The nanodrug was prepared by modifying Crocin-I with 4-pentylphenylboronic acid (PBA) and exhibited effective responsiveness and scavenging activity of reactive oxygen species. PBA-Crocin nanodrug displayed good biocompatibility and radioprotection effect compared to Crocin-I in vitro. The survival rate of cells treated with PBA-Crocin (10 µg mL-1) is comparable to that treated with amifostine (12.5 µg mL-1, the only radioprotector approved by the United States Food and Drug Administration clinically) after 6 Gy irradiation. Importantly, PBA-Crocin resulted in markedly prevention of radiation-induced damage in peripheral blood cells and a 1.6-fold longer retention time of Crocin-I in plasma in comparison with Crocin-I. The finding suggests a new design for natural medicine in effective radioprotection.

Anti-Phototoxicity Effect of Phenolic Compounds from Acetone Extract of Entada phaseoloides Leaves via Activation of COX-2 and iNOS in Human Epidermal Keratinocytes.

The extract from Entada phaseoloides was employed as active ingredients of natural origin into cosmetic products, while the components analysis was barely reported. Using LC-DAD-MS/qTOF analysis, eleven compounds (1-11) were proposed or identified from acetone extract of E. phaseoloides leaves (AE). Among them, six phenolic compounds, protocatechuic acid (2), 4-hydroxybenzoic acid (3), luteolin-7-O-ß-d-glucoside (5), cirsimaritin (6), dihydrokaempferol (9), and apigenin (10), were isolated by various chromatographic techniques. Protocatechuic acid (2), epicatechin (4), and kaempferol (11) at a concentration 100 µM increased the HaCaT cells viability of the UVB-irradiated cell without any cytotoxicity effect and reduced the expression of COX-2 and iNOS inflammation gene. Moreover, compounds 2 and 4 could have potent effects on cell migration during wound closure. These results suggest that compounds 2, 4, and 11 from AE have anti-photoaging properties and could be employed in pharmaceutical and cosmeceutical products.

Review on Natural Bioactive Products as Radioprotective Therapeutics: Present and Past Perspective.

Among conventional treatment methodologies, surgery, hyperthermia, radiation, and chemotherapy have become integral components of treatment for most cancers. Radiation therapy in the treatment of many malignancies is always the better choice over surgery and chemotherapy. Ionizing radiation produced as a consequence of using these radiations has always been a concern in these treatment methods. Synthetic radio-protectors with their inherent limitations are being used to date to reduce the mortality of these radiations; still, it compromises the clinical efficacy of these administrations. Hence, investigations for alternative methods, including natural resources such as plant and fruit extracts, are being explored to treat radiation-mediated ailments. The present review article endeavors to provide a comprehensive, updated, and chronological account of these promising plants and fruit extracts and their bioactive principles as radio-protectors. We present the merits and demerits of radiation therapy and cell stress generation of reactive oxygen species (ROS) associated with radiation need and availability of radio-protectors. Finally, we discuss green-based bioactive compounds that have radioprotective properties.

Yiqi Jiedu herbal decoction attenuates the 2 Gy 60Co γ ray induced spleen injury by inhibiting apoptosis and modulating the immune balance.

ETHNOPHARMACOLOGICAL RELEVANCE: Irradiation-induced immunosuppression often occurs during radiotherapy in patients, which would increase the risk of opportunistic infections. Many Chinese herbal prescriptions or natural extracts have recently attracted increased radiation protection and therapy attention due to their low toxicity. AIM OF THE STUDY: The present study aimed to investigate the protective effects of Yiqi Jiedu (YQJD) decoction on spleen injury induced by 2 Gy 60Co γ ray in mice. MATERIALS AND METHODS: A total of 180 Balb/c mice were randomly divided into five groups: blank control (Ctrl), model (IR), positive drug (IRA), low-dose YQJD decoction (IRL), and high-dose YQJD decoction (IRH). After a ten-day intervention, mice were exposed to a single dose of total body irradiation (2 Gy) and sacrificed on the 1st, 3rd, and 7th day after irradiation. The indicators include general observations and body weight, changes in peripheral hemogram, index and histopathology examination of the spleen, distribution of lymphocyte subsets, cytokine levels, and apoptosis in the spleen. RESULTS: In comparison to the Ctrl group, the body weight, spleen index, peripheral blood cell, and splenocyte quantities decreased significantly after exposure, accompanied by a notable increase of apoptosis in spleen cells. Moreover, ionizing radiation also broke the balance of CD4+/CD8+, Th1/Th2, and Th17/Treg, triggering immune imbalance and immunosuppression. The above injuries occurred on the 1st day after exposure, worsened on the 3rd, and were relieved on the 7th day. However, the pretreatment of YQJD decoction increased the spleen index, improved the spleen structure, and inhibited radiation-induced apoptosis after exposure. Additionally, YQJD decoction has shown its ability to promote immunological balance recovery following exposure by regulating CD4+/CD8+, Th1/Th2, and Th17/Treg ratios, which may minimize the risk of infection. In addition, the high-dose of YQJD decoction showed a better protective effect than the low-dose group. CONCLUSION: The protective effects of YQJD decoction on 2 Gy 60Coγray induced spleen injury were confirmed in this study. This mechanism may be related to inhibiting apoptosis and modulating immune balance. This exploration might provide new insights into the use of Chinese herbs on radioprotection of the immune system.

Podophyllum hexandrum and its active constituents: Novel radioprotectants.

Human exposure to radiation has expanded considerably in recent years, due to a wide range of medical, agricultural, and industrial applications. Despite its beneficial utilities, radiation is also known to have a deleterious effect on cells and tissues, largely through the creation of free radicals, which cause severe damage to biological systems through processes such as DNA double/single-strand fragmentation, protein modification, and upregulation of lipid peroxidation pathways. In addition, radiation damages genetic material while inducing hereditary genotoxicity. Developing measures to counter radiation-induced damage is thus considered to be of significant importance. Considering the inherent capability of plants to survive radiative conditions, certain plants and natural compounds have been the subject of investigations to explore and harness their natural radioprotective abilities. Podophyllum hexandrum, an Indian medicinal plant with several known traditional phytotherapeutic uses, is considered in particular to be of immense therapeutic importance. Recent studies have been conducted to validate its radioprotective potential alongside discovering its protective mechanisms following γ-radiation-induced mortality and disorder in both mice and human cells. These findings show that Podophyllum and its constituents/natural compounds protect the lungs, gastrointestinal tissues, hemopoietic system, and testis by inducing DNA repair pathways, apoptosis inhibition, free radical scavenging, metal chelation, anti-oxidation and anti-inflammatory mechanisms. In this review, we have provided an updated, comprehensive summary of ionizing radiations and their impacts on biological systems, highlighting the mechanistic and radioprotective role of natural compounds from Podophyllum hexandrum.

Ferulago angulata as a Good Radioprotector Against Genotoxicity.

INTRODUCTION: Natural products can be used as radioprotector agents because of containing phenolic compounds and several flavonoids with antioxidant properties. When the normal cells are exposed to ionizing radiation, they generate free radicals and reactive oxygen species that can cause damage in DNA, which leads to cellular dysfunction or even cell death. However, it is necessary to identify new radioprotective agents to protect normal cells. Ferulago angulata (F. angulata), a medicinal plant, can be used as a new radioprotective agent. PURPOSE: In this study, the radioprotective effect of F. angulata was evaluated against genotoxicity and oxidative stress induced by ionizing radiation in human blood lymphocytes. METHODS: The antioxidant activity of F. angulata was assayed using FRAP and DPPH methods. Then, the human blood samples were incubated with F. angulata at different concentrations (25, 50, 100, and 200 µM) and subsequently exposed to IR at a dose of 2Gy. The radioprotective effect of F. angulata on the exposed cells was assessed by the micronucleus (MN) method. Also, biomarkers of oxidative stress in the exposed cells were evaluated by malondialdehyde (MDA) and superoxide dismutase (SOD) methods. RESULTS: Our findings showed that F. angulata reduced the frequency of MN induced by IR in exposed cells. At a 200 µM concentration of F. angulata, the maximum reduction in the frequency of MN (63.11%) was observed that demonstrated a high degree of radioprotection. Afterward, pretreatment at 200 µM concentration of F. angulata inhibited oxidative stress in irradiated lymphocytes, leading to a reduction in MN frequency and MDA levels while SOD activity was enhanced in the exposed cells. CONCLUSION: F. angulata as a natural radioprotective agent can protect normal cells against reactive oxygen species and genetic damage induced by IR.

Comparative study of the photo­protective and anti­melanogenic properties of gomisin D, J and O.

Skin cancer is the most common human malignancy worldwide and solar ultraviolet (UV) radiation is known to serve an important role in its pathogenesis. Natural candidate compounds with antioxidant, photoprotective and anti­melanogenic effects were investigated against the background of skin photoprotective and anti­melanogenic properties. Gomisin D, J and O are dibenzocyclooctadiene lignans present in Kadsura medicinal plants and possess several pharmacological activities. In this study, the functions and mechanisms underlying the effects of gomisin D, J and O in UVA­and UVB­irradiated keratinocytes and α­melanocyte stimulating hormone (α­MSH)­stimulated melanocytes were explored. Following UVA and UVB irradiation, keratinocytes were treated with gomisin D, J and O, and keratinocyte viability, lactate dehydrogenase (LDH) release, intracellular reactive oxygen species (ROS) production and apoptosis were examined. The results demonstrated that gomisin D and J improved keratinocyte viability and reduced LDH release under UVA and UVB irradiation. Intracellular ROS production induced by UVA and UVB irradiation was suppressed by gomisin D and J. In addition, Annexin V and TUNEL staining analysis indicated that gomisin D and J have significant anti­apoptotic effects on UVA­and UVB­irradiated keratinocytes. After α­MSH stimulation, melanocytes were treated with gomisin D, J and O, and the changes in melanocyte viability, intracellular melanin content, intracellular tyrosinase activity, and mechanisms underlying these changes were examined. Gomisin D markedly inhibited the α­MSH­induced increase in intracellular melanin content and tyrosinase activity. Mechanistically, gomisin D reduced the protein and mRNA expression levels of microphthalmia­associated transcription factor (MITF), tyrosinase, tyrosinase­related protein (TRP)­1 and TRP­2 in α­MSH­stimulated melanocytes. In addition, gomisin D markedly downregulated α­MSH­induced phosphorylation of protein kinase A and cAMP response element binding protein, which are known to be present upstream of the MITF, tyrosinase, TRP­1 and TRP­2 genes. Overall, gomisin D has photoprotective and anti­melanogenic effects; these findings provide a basis for the production of potential brightening and photoprotective agents using natural compounds such as gomisin D.

Curcumins antineoplastic, radiosensitizing and radioprotective properties.

BACKGROUND: Curcumin is an ingredient in the turmeric plant that gives yellow color to dishes and is used as a spice. It has been used locally/topically and systemically in the treatment of diseases in Far Eastern societies, especially in Indian and Chinese traditional medicine. Curcumin is a natural substance that does not show toxic properties in overdose. In addition to its anti-inflammatory, anti-oxidant, anti-neoplastic, anti-viral, anti-microbial, anti-angiogenic properties, platelet aggregation, apoptosis, and wound healing have been demonstrated in different studies. In recent years, it has been used as a radiosensitizing agent and a radioprotector in radiation therapy. Although curcumin has low bio-availability, it seems to be the ideal molecule due to its low molecular weight, high activity in inhibiting the growth of tumor cells and protecting normal tissues from the side effects of radiation. PURPOSE: Curcumin in combination with radiotherapy was discussed in the light of the literature.

The potent radioprotective agents: Novel nitronyl nitroxide radical spin-labeled resveratrol derivatives.

It is commonly known that radiotherapy is still a key modality for treatment of cancer. Though this effect is desirable during radiotherapy, it leads to radiotoxicity on normal healthy cells. In the present research, we designed, synthesized and analyzed a series of nitronyl nitroxide radical (NITR) spin-labeled resveratrol (RES) derivatives. The cytotoxicity of the newly synthesized substances was tested on Jurkat T cells. The derivatives were studied as reactive oxygen species (ROS) scavenger to protect ionizing radiation of Jurkat T cells upon 6 Gy X-irradiation. The experimental results revealed that compound 2 and 3 could significantly alleviate the damage of Jurkat T cells, as evidenced by decreasing ROS production and restoring the cell apoptosis. Further mechanism investigations indicated that the radioprotective effects of the novel derivatives were largely associated with modulating the expression of apoptotic proteins including cIAP-1, cIAP-2, cytochrome c, caspase-3 and caspase-9. Based on the experimental result, we disclosed that the novel NITR spin-labeled RES derivatives exhibit the potential to be used as the novel radioprotective candidates to ameliorate the injury induced by ionizing radiation.