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Oxyresveratrol (OxyR) exerts biological and pharmacological effects in a variety of tumor cells, including antioxidant action, antitumor activity, and proapoptotic effects. However, the regulation of targeted signaling pathways by OxyR and the mechanism underlying these effects in human renal cell carcinoma (RCC) have been less studied. We observed that OxyR at noncytotoxic doses did not affect the growth of human RCC cells or normal kidney HK2 cells. OxyR inhibited ACHN and Caki‐1 cell migration and invasion through targeting matrix metalloproteinase 1 (MMP1) expression. Analysis of clinical databases showed that high MMP1 expression is associated with lower overall survival (OS) in these cancers (p < 0.01). OxyR significantly inhibited the mRNA and protein expression of Sp1. Furthermore, luciferase assay results showed that OxyR inhibited Sp1 transcriptional activity. Additionally, OxyR preferentially suppressed the activation of ERK and PKCα. Treatment with U0126 (MEK inhibitor) or G06976 (PKCα inhibitor) clearly decreased Sp1 and MMP1 expression and inhibited RCC cell migration and invasion. In conclusion, OxyR may be a potential antitumor therapy for the inhibition of migration and invasion by controlling p‐ERK/Sp1 and p‐PKCα/Sp1‐mediated MMP1 expression in RCC. [ABSTRACT FROM AUTHOR]

Resveratrol (trans-3,5,4′-trihydroxystilbene, RES) is one of the most well-known natural products with numerous health benefits. To explore the nutraceutical potentials of some dietary RES derivatives including isorhapontigenin (trans-3,5,4′-trihydroxy-3′-methoxystilbene, ISO), oxyresveratrol (trans-3,5,2′,4′-tetrahydroxystilbene, OXY) and pterostilbene (trans-3,5-dimethoxy-4′-hydroxystilbene, PTS), their impacts on metabolism and health were assessed in Sprague Dawley rats after a two-week daily oral administration at the dose of 100 µmol/kg/day. Non-targeted metabolomic analyses were carried out with the liver, heart, brain and plasma samples using gas chromatography–tandem mass spectrometry (GC-MS/MS). Notable in vivo health benefits were observed, as the rats received ISO, PTS or RES showed less body weight gain; the rats received OXY or RES displayed healthier fasting blood glucose levels; while all of the tested stilbenes exhibited cholesterol-lowering effects. Additionally, many important metabolic pathways such as glycolysis, pentose phosphate pathway, tricarboxylic acid cycle and fatty acid oxidation were found to be modulated by the tested stilbenes. Besides the reaffirmation of the well-known beneficial effects of RES in diabetes, obesity, cardiovascular disease and Alzheimer's disease, the metabolomic analyses also suggest the anti-diabetic, cardio-, hepato- and neuro-protective activities of ISO; the anti-diabetic, cardio-, hepato- and neuro-protective effects of OXY; and the anti-aging, anti-inflammatory, cardio-, hepato- and neuro-protective potential of PTS. Interestingly, although these stilbenes share a similar structure, their biological activities appear to be distinct. In conclusion, similarly to RES, ISO, OXY and PTS have emerged as promising candidates for further nutraceutical development. [ABSTRACT FROM AUTHOR]

Epithelial ovarian carcinoma poses a significant challenge due to its resistance to chemotherapy and propensity for metastasis, thereby reducing the effectiveness of conventional treatments. Hence, the identification of novel compounds capable of augmenting the anti-cancer efficacy of platinum-based chemotherapy is imperative. Oxyresveratrol (OXY), a derivative of resveratrol, has been demonstrated to possess antiproliferative and apoptosis-inducing effects across various cancer cell lines. Notably, OXY appears to exert its effects by inhibiting the PI3K/AKT/mTOR signaling pathway. However, the synergistic potential of OXY in combination with cisplatin against epithelial ovarian cancer has not yet been elucidated. The current study investigated the synergistic effects of OXY and cisplatin on the ovarian cancer cell lines SKOV3 and TOV21G. We found that OXY significantly enhanced cisplatin's ability to reduce cell viability, induce apoptosis, induce cell cycle arrest, and increase the proportion of cells in the sub-G1 phase. Furthermore, OXY treatment alone dose-dependently inhibited the production of anti-apoptotic proteins including Mcl-1, Bcl-xL, and XIAP under EGF activation. Mechanistically, OXY suppressed the PI3K/AKT/mTOR signaling pathway by reducing phosphorylated AKT, while having no discernible effect on the MAPK pathway. These findings highlight OXY's potential to enhance ovarian cancer cell sensitivity to chemotherapy, suggesting its development as a pharmaceutical adjunct for clinical use in combination therapies. [ABSTRACT FROM AUTHOR]

Oxyresveratrol is a stilbene compound with a simple chemical structure and various therapeutic potentials. This study summarized and analyzed the multiple pharmacological effects and mechanisms of oxyresveratrol, identifying its prominent performance in neuroprotection, hepatoprotection, and anti-inflammatory activities in the intestines. By integrating the pharmacological effects of oxyresveratrol with insights from the network pharmacology and molecular docking of its interactions with targets linked to gut–liver–brain axis disorders, it has been shown that oxyresveratrol may hold promise for the treatment of gut–liver–brain axis-related disorders. The synergistic effect between various mechanisms has inspired further research and the development of oxyresveratrol's application value. [ABSTRACT FROM AUTHOR]

Breast cancer is the second most common type of cancer in the world. Polyphenols can act at all stages of carcinogenesis and oxyresveratrol (OXY) promising anticancer properties, mainly associated with chemotherapy drugs. The aim of this study was to investigate the effect of OXY with doxorubicin (DOX) or melphalan (MEL), either isolated or associated, in MCF-7 and MDA-MB-231 breast cancer cells. Our results showed that OXY, DOX, and MEL presented cytotoxicity, in addition to altering cell morphology. The synergistic association of OXY + DOX and OXY + MEL reduced the cell viability in a dose-dependent manner. The OXY, DOX, or MEL and associations were able to alter the ROS production, ∆Ψm, and cell cycle; DOX and OXY + DOX led the cells to necrosis. Furthermore, OXY and OXY + MEL were able to lead the cells to apoptosis and upregulate caspases-3, -7, -8, and -9 in both cells. LC-HRMS showed that 7-deoxidoxorubicinone and doxorubicinol, responsible for the cardiotoxic effect, were not identified in cells treated with the OXY + DOX association. In summary, our results demonstrate for the first time the synergistic effect of OXY with chemotherapeutic agents in breast cancer cells, offering a new strategy for future animal studies. [ABSTRACT FROM AUTHOR]

Inflammatory responses and oxidative stress damage the integrity of the blood-brain barrier (BBB), which is a primary pathological modulator of neurodegenerative diseases. Brain endothelial cells are crucial components of BBB. In the present study, the effect of oxyresveratrol on lipopolysaccharide (LPS)-induced brain endothelial (bEnd.3) cells was assessed. Our results showed that oxyresveratrol diminished protein expressions of inducible nitric oxide synthase (iNOS) and adhesion molecules including intercellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), nitric oxide (NO) production, and proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor (TNF-α) in LPS-elicited bEnd.3 cells. These anti-inflammatory effects were mediated through suppressing nuclear factor-kappa B (NF-κB) and mitogen-activated protein kinase (MAPK) signaling pathways. In addition, we found that oxyresveratrol reduced reactive oxygen species (ROS) levels. To conclude, the current results demonstrated the protective role of oxyresveratrol against LPS-induced inflammation and oxidative stress in bEnd.3 cells, suggesting its potential effect for mitigating neurodegenerative and cerebrovascular diseases.

Mulberry (Morus alba L.) twigs are a traditional Chinese medicine and edible agricultural by-product. Oxyresveratrol (OXY) is one of the natural resorcinol-type polyphenols obtained from mulberry twigs with anti-melanogenesis effects. This study aimed to investigate the ameliorative effects and mechanisms of OXY on post-inflammatory hyperpigmentation (PIH) in vitro. The results of DPPH radical scavenging and tyrosinase inhibition assays showed that OXY exhibited potent antioxidant and tyrosinase inhibitory activities. In human melanocytes, OXY significantly down-regulated protein expression related to melanin synthesis and transport. A molecular docking study suggested that OXY could inhibit these GTPases (RAB27A, RAC1, and CDC42) activities in melanosome transfer processes. Furthermore, OXY significantly reduced inflammatory factor secretion, promoted human β-defensin production, and up-regulated the expression of barrier proteins in UVB-induced human keratinocytes. This research indicated that the OXY from mulberry twigs has potential applications in ameliorating PIH through its antioxidant, anti-melanogenic, melanosome transport inhibition, anti-inflammatory, and photoprotective properties.

Abstract Alzheimer’s disease (AD) is associated with cognitive deficits and epigenetic deacetylation that can be modulated by natural products. The role of natural oxyresveratrol-β-cyclodextrin (ORV) on cognition and histone deacetylase activity in AD is unclear. Herein, in-silico docking and molecular dynamics simulation analysis determined that oxyresveratrol potentially targets histone deacetylase-2 (HDAC2). We therefore evaluated the in vivo ameliorative effect of ORV against cognitive deficit, cerebral and hippocampal expression of HDAC in experimental AD rats. Intracerebroventricular injection of STZ (3 mg/kg) induced experimental AD and the rats were treated with low dose (200 mg/kg), high dose (400 mg/kg) of ORV and donepezil (10 mg/kg) for 21 days. The STZ-induced AD caused cognitive and behavioural deficits demonstrated by considerable increases in acetylcholinesterase activity and escape latency compared to sham control. The levels of malondialdehyde (MDA) and HDAC activity were significantly increased in AD disease group comparison to the sham. Interestingly, the ORV reversed the cognitive-behavioural deficit and prominently reduced the MDA and HDAC levels comparable to the effect of the standard drug, donepezil. The findings suggest anti-AD role of ORV via antioxidant effect and inhibition of HDAC in the hippocampal and frontal cortical area of rats for AD.

This study aimed to isolate and purify resveratrol and oxyresveratrol from the heartwoods of Maclura cochinchinensis, and to evaluate their inhibitory effects on melanogenesis in B16F10 murine melanoma cells. A methanol maceration process yielded a crude extract comprising 24.86% of the initial mass, which was subsequently analyzed through HPTLC, HPLC, and LC-MS/MS. These analyses revealed the presence of resveratrol and oxyresveratrol at concentrations of 4.32 mg/g and 33.6 mg/g in the extract, respectively. Initial purification employing food-grade silica gel column chromatography separated the extract into two fractions: FA, exhibiting potent inhibition of both tyrosinase activity and melanogenesis, and FM, showing no such inhibitory activity. Further purification processes led to the isolation of fractions Y11 and Gn12 with enhanced concentrations of resveratrol (94.9 and 110.21 mg/g, respectively) and fractions Gn15 and Gn16 with elevated levels of oxyresveratrol (321.93 and 274.59 mg/g, respectively), all of which significantly reduced melanin synthesis. These outcomes affirm the substantial presence of resveratrol and oxyresveratrol in the heartwood of M. cochinchinensis, indicating their promising role as natural agents for skin lightening. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is associated with cognitive deficits and epigenetic deacetylation that can be modulated by natural products. The role of natural oxyresveratrol-β-cyclodextrin (ORV) on cognition and histone deacetylase activity in AD is unclear. Herein, in-silico docking and molecular dynamics simulation analysis determined that oxyresveratrol potentially targets histone deacetylase-2 (HDAC2). We therefore evaluated the in vivo ameliorative effect of ORV against cognitive deficit, cerebral and hippocampal expression of HDAC in experimental AD rats. Intracerebroventricular injection of STZ (3 mg/kg) induced experimental AD and the rats were treated with low dose (200 mg/kg), high dose (400 mg/kg) of ORV and donepezil (10 mg/kg) for 21 days. The STZ-induced AD caused cognitive and behavioural deficits demonstrated by considerable increases in acetylcholinesterase activity and escape latency compared to sham control. The levels of malondialdehyde (MDA) and HDAC activity were significantly increased in AD disease group comparison to the sham. Interestingly, the ORV reversed the cognitive-behavioural deficit and prominently reduced the MDA and HDAC levels comparable to the effect of the standard drug, donepezil. The findings suggest anti-AD role of ORV via antioxidant effect and inhibition of HDAC in the hippocampal and frontal cortical area of rats for AD. [ABSTRACT FROM AUTHOR]

Oxyresveratrol (ORV) is naturally found in Artocapus lakoocha Roxb. (AL), similar to resveratrol. This AL extract has demonstrated considerable importance in dietary supplements and cosmetics for its anti-tyrosinase and antioxidant properties. There is a great demand for ORV in the cosmetic and pharmaceutical industries. Traditionally, harsh solvents have been used to extract ORV from AL. This study aims to address this issue by introducing green technology with a ready-to-use extract for the enrichment of ORV extraction from AL using deep eutectic solvents (DESs). Thirty-three DESs were synthesized and characterized. The extraction efficiency of these DESs was evaluated by ORV content (g ORV/kg dried plant) and compared with the conventional solvents, analyzed by validated HPLC. Notably, two synthesized DESs, namely choline chloride/citric acid/water (2:1:3) (DES10) and choline chloride/xylose (1:1) (DES17), showed higher ORV content than the conventional solvents and were therefore selected for optimization of extraction conditions using Box–Behnken designs, considering three variable levels: time, temperature, and water as co-solvents. Interestingly, the biological activities of ORV-enriched extracts from DES10 and DES17 were evaluated, and the results showed that they were 74-fold and 252-fold more potent than kojic acid in terms of tyrosinase inhibitory activity. DES17 was 17-fold more potent antioxidants than ascorbic acid. The morphology of AL powder before and after extraction with DESs under SEM suggested that DESs have the same mechanism as classical organic solvents. These ORV-enriched extracts can be directly incorporated into cosmetic formulations and production scales without the need to prepare a stock solution and are therefore referred to as ready-to-use extracts. This study successfully pioneered the use of DESs for environmentally friendly and highly efficient ORV extraction from AL to produce ready-to-use extracts and applications for the pharmaceutical and cosmetic industries. [ABSTRACT FROM AUTHOR]

The rich chemical constituents and diverse pharmacological properties of Ramulus Mori (RM) or the twig of Morus alba with evidence supported by clinical trials and patents are reviewed. Known as Sangzhi in Chinese, RM is widely used in traditional Chinese medicine to treat gout, arthritis, and rheumatism. Chemical constituents include flavonoids, benzofurans, alkaloids, stilbenes, chalcones, phenolic acids, and coumarins. Bioactivities of RM include antidiabetic, anti-obesity, anti-inflammatory, antityrosinase, neuroprotective, antioxidant, hepatoprotective, cytoprotective, renoprotective, antihyperuricemic, analgesic, antifungal, DNA protective, anticancer, gastroprotective, cardioprotective, anti-hair aging, anti-arthritic, and antiplatelet aggregation properties. The most active compounds from RM are mulberrin, oxyresveratrol, and mulberroside A. All four clinical trials on RM are focused on the treatment of diabetes. The patents entail using RM extracts as cosmetics for skin whitening and as agents for hypoglycemia. Topics for further research on RM are suggested.

Abstract Background Bone is continuously produced by osteoblasts and resorbed by osteoclasts to maintain homeostasis. Impaired bone resorption by osteoclasts causes bone diseases such as osteoporosis and arthritis. Most pharmacological treatment of osteoporosis focuses on inhibiting osteoclast differentiation, often to restore osteoclast/osteoclast balance. However, recent osteoporosis treatments have various side effects. According to a recent study, resveratrol, known as a stilbenoid family, is known to increase bone density, and the osteoclast inhibitory effect was confirmed using oxyresveratrol, a stilbenoid family. Here, we investigated the effect of oxyresveratrol on osteoclast differentiation and an ovariectomized mouse model. Methods Mouse leukemia monocyte/macrophage cell line RAW 264.7 was treated with oxyresveratrol, and cell cytotoxicity was confirmed by measuring MTT assay. Tartrate-resistant acid phosphatase (TRAP), an enzyme marker for osteoclasts, was confirmed by staining. In addition, osteoclast differentiation markers and MAPK-related markers were confirmed at the mRNA level and protein expression. The effect of oxyresveratrol was confirmed using ovariectomized mice. Deoxypyridinoline (DPD) was measured using mouse urine and TRAP activity was observed using serum. Bone mineral density was also measured using Micro-CT. Results The polyphenol oxyresveratrol inhibited receptor activator of nuclear factor kappa-Β ligand (RANKL)-induced osteoclast differentiation of RAW 264.7 cells. Furthermore, oxyresveratrol inhibited TRAP activity and actin-ring formation. Moreover, oxyresveratrol suppressed the phosphorylation of the RANKL-induced mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK and significantly reduced the expression of bone differentiation markers (NFATc1, cathepsin K, and TRAP). Conclusion Oxyresveratrol inhibits osteoclast differentiation via MAPK and increases bone density in ovariectomized rats, suggesting it has therapeutic potential for bone diseases such as osteoporosis. We confirmed the osteoporosis prevention effect of OR in Raw 264.7 cells, and future studies should confirm the effect of OR using rat bone marrow-derived cells.

Oxyresveratrol is one of the active ingredients derived from mulberry branch with strong anti-inflammatory bioactivity. In this research, we want to explore if oxyresveratrol can improve cognitive impairments and episodic-like memory and its mechanism. In LPS-induced BV-2 cells, 25 μM OXY can significantly inhibit the expression of NO and alter the M1/M2 polarization by regulating M1/M2 phenotype makers. In vivo, OXY (50, 100 mg/kg) significantly reversed cognitive impairments and alleviated neuronal injuries caused by neuroinflammation. According to network pharmacology analysis, OXY alleviated neuroinflammation via the PI3K-Akt pathway. In general, the research revealed that OXY can improve cognitive impairments and episodic-like memory through alleviating LPS-induced neuroinflammation and regulating the PI3K-Akt signaling pathway. [ABSTRACT FROM AUTHOR]

Epithelial ovarian carcinoma poses a significant challenge due to its resistance to chemotherapy and propensity for metastasis, thereby reducing the effectiveness of conventional treatments. Hence, the identification of novel compounds capable of augmenting the anti-cancer efficacy of platinum-based chemotherapy is imperative. Oxyresveratrol (OXY), a derivative of resveratrol, has been demonstrated to possess antiproliferative and apoptosis-inducing effects across various cancer cell lines. Notably, OXY appears to exert its effects by inhibiting the PI3K/AKT/mTOR signaling pathway. However, the synergistic potential of OXY in combination with cisplatin against epithelial ovarian cancer has not yet been elucidated. The current study investigated the synergistic effects of OXY and cisplatin on the ovarian cancer cell lines SKOV3 and TOV21G. We found that OXY significantly enhanced cisplatin’s ability to reduce cell viability, induce apoptosis, induce cell cycle arrest, and increase the proportion of cells in the sub-G1 phase. Furthermore, OXY treatment alone dose-dependently inhibited the production of anti-apoptotic proteins including Mcl-1, Bcl-xL, and XIAP under EGF activation. Mechanistically, OXY suppressed the PI3K/AKT/mTOR signaling pathway by reducing phosphorylated AKT, while having no discernible effect on the MAPK pathway. These findings highlight OXY’s potential to enhance ovarian cancer cell sensitivity to chemotherapy, suggesting its development as a pharmaceutical adjunct for clinical use in combination therapies.

Oxyresveratrol is a stilbene compound with a simple chemical structure and various therapeutic potentials. This study summarized and analyzed the multiple pharmacological effects and mechanisms of oxyresveratrol, identifying its prominent performance in neuroprotection, hepatoprotection, and anti-inflammatory activities in the intestines. By integrating the pharmacological effects of oxyresveratrol with insights from the network pharmacology and molecular docking of its interactions with targets linked to gut–liver–brain axis disorders, it has been shown that oxyresveratrol may hold promise for the treatment of gut–liver–brain axis-related disorders. The synergistic effect between various mechanisms has inspired further research and the development of oxyresveratrol’s application value.

Breast cancer is the second most common type of cancer in the world. Polyphenols can act at all stages of carcinogenesis and oxyresveratrol (OXY) promising anticancer properties, mainly associated with chemotherapy drugs. The aim of this study was to investigate the effect of OXY with doxorubicin (DOX) or melphalan (MEL), either isolated or associated, in MCF-7 and MDA-MB-231 breast cancer cells. Our results showed that OXY, DOX, and MEL presented cytotoxicity, in addition to altering cell morphology. The synergistic association of OXY + DOX and OXY + MEL reduced the cell viability in a dose-dependent manner. The OXY, DOX, or MEL and associations were able to alter the ROS production, ∆Ψm, and cell cycle; DOX and OXY + DOX led the cells to necrosis. Furthermore, OXY and OXY + MEL were able to lead the cells to apoptosis and upregulate caspases-3, -7, -8, and -9 in both cells. LC-HRMS showed that 7-deoxidoxorubicinone and doxorubicinol, responsible for the cardiotoxic effect, were not identified in cells treated with the OXY + DOX association. In summary, our results demonstrate for the first time the synergistic effect of OXY with chemotherapeutic agents in breast cancer cells, offering a new strategy for future animal studies.

This study aimed to isolate and purify resveratrol and oxyresveratrol from the heartwoods of Maclura cochinchinensis, and to evaluate their inhibitory effects on melanogenesis in B16F10 murine melanoma cells. A methanol maceration process yielded a crude extract comprising 24.86% of the initial mass, which was subsequently analyzed through HPTLC, HPLC, and LC-MS/MS. These analyses revealed the presence of resveratrol and oxyresveratrol at concentrations of 4.32 mg/g and 33.6 mg/g in the extract, respectively. Initial purification employing food-grade silica gel column chromatography separated the extract into two fractions: FA, exhibiting potent inhibition of both tyrosinase activity and melanogenesis, and FM, showing no such inhibitory activity. Further purification processes led to the isolation of fractions Y11 and Gn12 with enhanced concentrations of resveratrol (94.9 and 110.21 mg/g, respectively) and fractions Gn15 and Gn16 with elevated levels of oxyresveratrol (321.93 and 274.59 mg/g, respectively), all of which significantly reduced melanin synthesis. These outcomes affirm the substantial presence of resveratrol and oxyresveratrol in the heartwood of M. cochinchinensis, indicating their promising role as natural agents for skin lightening.

Oxyresveratrol (ORV) is naturally found in Artocapus lakoocha Roxb. (AL), similar to resveratrol. This AL extract has demonstrated considerable importance in dietary supplements and cosmetics for its anti-tyrosinase and antioxidant properties. There is a great demand for ORV in the cosmetic and pharmaceutical industries. Traditionally, harsh solvents have been used to extract ORV from AL. This study aims to address this issue by introducing green technology with a ready-to-use extract for the enrichment of ORV extraction from AL using deep eutectic solvents (DESs). Thirty-three DESs were synthesized and characterized. The extraction efficiency of these DESs was evaluated by ORV content (g ORV/kg dried plant) and compared with the conventional solvents, analyzed by validated HPLC. Notably, two synthesized DESs, namely choline chloride/citric acid/water (2:1:3) (DES10) and choline chloride/xylose (1:1) (DES17), showed higher ORV content than the conventional solvents and were therefore selected for optimization of extraction conditions using Box–Behnken designs, considering three variable levels: time, temperature, and water as co-solvents. Interestingly, the biological activities of ORV-enriched extracts from DES10 and DES17 were evaluated, and the results showed that they were 74-fold and 252-fold more potent than kojic acid in terms of tyrosinase inhibitory activity. DES17 was 17-fold more potent antioxidants than ascorbic acid. The morphology of AL powder before and after extraction with DESs under SEM suggested that DESs have the same mechanism as classical organic solvents. These ORV-enriched extracts can be directly incorporated into cosmetic formulations and production scales without the need to prepare a stock solution and are therefore referred to as ready-to-use extracts. This study successfully pioneered the use of DESs for environmentally friendly and highly efficient ORV extraction from AL to produce ready-to-use extracts and applications for the pharmaceutical and cosmetic industries.

Death‐associated protein kinase 1 (DAPK1), a Ca2+/calmodulin‐regulated serine/threonine kinase, regulates cell apoptosis and autophagy and has been implicated in the pathogenesis of Alzheimer's disease (AD). Targeting DAPK1 may be a promising approach for treating AD. In our previous study, we found that a natural polyphenol, resveratrol (1), is a moderate DAPK1 inhibitor. In the present study, we investigated the interactions between natural and synthetic derivatives of 1 and DAPK1. Binding assays including intrinsic fluorescence quenching, protein thermal shift and isothermal titration calorimetry indicated that oxyresveratrol (3), a hydroxylated derivative, and pinostilbene (5), a methoxylated derivative, bind to DAPK1 with comparable affinity to 1. The enzymatic assay showed that 3 more effectively inhibits the intrinsic ATPase activity of DAPK1 compared with 1. Crystallographic analysis revealed that the binding modes of the methoxylated derivatives were different from those of 1 and 3, resulting in a unique interaction. Our results suggest that 3 may be helpful in treating AD and provide a clue for the development of promising DAPK1 inhibitors. [ABSTRACT FROM AUTHOR]

Artocarpus lacucha, a plant in the Moraceae family, has traditionally been used in Southeast Asian medicine to treat various ailments. This study investigated the insecticidal potential against Spodoptera litura of several compounds extracted from A. lacucha using a topical application method. A sequential extraction method was employed with A. lacucha stems to identify the most toxic crude extract by using hexane, dichloromethane, ethyl acetate, and methanol solvents. Subsequently, the most toxic crude extract was analyzed for chemical composition by HPLC, followed by the isolation process. Among these crude extracts, the ethyl acetate crude extract was the most toxic to second-instar S. litura larvae (24-h LD50 value of ∼9.07 µg/larva). Our results showed that the catechin isolated from the ethyl acetate crude extract exhibited the highest toxicity against this insect (24-h LD50 value of ∼8.37 µg/larva). Additionally, catechin significantly decreased the activities of acetylcholinesterase, carboxylesterases, and glutathione S-transferase in the larvae. These findings suggest that catechin isolated from A. lacucha could be a potential insecticidal agent against S. litura. However, the toxicity and persistence of catechin under field conditions need to be further investigated to develop this novel insecticide. [ABSTRACT FROM AUTHOR]

Oxyresveratrol (ORV) is one of the novel antioxidants having been extensively studied in recent years. One of the main sources of ORV is Artocarpus lakoocha, which has been used in traditional medicine in Thailand for decades. However, the role of ORV in skin inflammation has not been clearly demonstrated. Therefore, we investigated the anti-inflammatory effects of ORV on dermatitis model. The effect of ORV was examined on human immortalized and primary skin cells exposed to bacterial components including peptidoglycan (PGN) and lipopolysaccharide (LPS) and 2,4-Dinitrochlorobenzene (DNCB)-induced dermatitis mouse model. PGN and LPS were used to induce inflammation on immortalized keratinocytes (HaCaT) and human epidermal keratinocytes (HEKa). We then performed MTT assay, Annexin V and PI assay, cell cycle analysis, real-time PCR, ELISA and Western blot in these in vitro models. H&E staining, immunohistochemistry (IHC) staining with CD3, CD4 and CD8 markers were used to evaluate the effects of ORV in in vivo model of skin inflammation using BALB/c mice. Pretreatment of HaCaT and HEKa cells with ORV inhibited pro-inflammatory cytokine production through inhibition of NF-κB pathway. In DNCB-induced dermatitis mouse model, ORV treatment reduced lesion severity, and skin thickness and numbers of CD3, CD4 and CD8 T cells in the sensitized skin of mice. In conclusion, it has been demonstrated that ORV treatment can ameliorate inflammation in the in vitro models of skin inflammation and in vivo models of dermatitis, suggesting a therapeutic potential of ORV for treatment of skin diseases particularly eczema. [ABSTRACT FROM AUTHOR]

The white mulberry (Morus alba L.) is widely used as a medicinal plant in Asia. In this study, the bioactive compounds of ethanolic extracts of white mulberry leaves from the Sakon Nakhon and Buriram cultivars were evaluated. The ethanolic extracts of mulberry leaves from the Sakon Nakhon cultivar showed the highest total phenolic content of 49.68 mg GAE/g extract and antioxidant activities of 4.38 mg GAE/g extract, 4.53 mg TEAC/g extract, and 92.78 mg FeSO4/g extract using 2,2 diphenyl-1-picrylhydrazyl (DPPH), 2,20-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays, respectively. The resveratrol and oxyresveratrol compounds in mulberry leaves were also investigated by high-performance liquid chromatography (HPLC). The mulberry leaf extracts from the Sakon Nakhon and Buriram cultivars showed oxyresveratrol contents of 1.20 ± 0.04 mg/g extract and 0.39 ± 0.02 mg/g extract, respectively, whereas resveratrol was not detected. It was also found that the potent anti-inflammatory properties of mulberry leaf extracts and its compounds, resveratrol and oxyresveratrol, suppressed the LPS-stimulated inflammatory responses in RAW 264.7 macrophage cells by significantly reducing nitric oxide production in a concentration-dependent manner. These compounds further inhibited interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production and suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophage cells. Therefore, it is established that mulberry leaf extract and its bioactive compounds contribute to its anti-inflammatory activity. [ABSTRACT FROM AUTHOR]

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Oxyresveratrol is one of the active ingredients derived from mulberry branch with strong anti-inflammatory bioactivity. In this research, we want to explore if oxyresveratrol can improve cognitive impairments and episodic-like memory and its mechanism. In LPS-induced BV-2 cells, 25 μM OXY can significantly inhibit the expression of NO and alter the M1/M2 polarization by regulating M1/M2 phenotype makers. In vivo, OXY (50, 100 mg/kg) significantly reversed cognitive impairments and alleviated neuronal injuries caused by neuroinflammation. According to network pharmacology analysis, OXY alleviated neuroinflammation via the PI3K-Akt pathway. In general, the research revealed that OXY can improve cognitive impairments and episodic-like memory through alleviating LPS-induced neuroinflammation and regulating the PI3K-Akt signaling pathway.

Objective: Hypoxia in the pulpitis process, the use of bleaching agents, and resin-containing materials produce reactive oxygen species. Their damage to the pulp tissue can be eliminated by melatonin and oxyresveratrol. However, the cytotoxic effects of these antioxidants on dental pulp stem cells are not well known. The aim of this study was to observe the cytotoxic effects of melatonin and oxyresveratrol for 72 hours on dental pulp stem cells. Materials and Methods: Human dental pulp stem cells obtained from the American Type Culture Collection were seeded on E-Plates®, and after 24 hours, 3 different doses of melatonin (100 pM, 100 nM, and 100 µM) and oxyresveratrol (10 µM, 25 µM, and 50 µM) were added. Real-time cell index data was acquired by using xCELLigence® device for 72 hours and inhibitor concentration (IC50) values of experimental groups were obtained. Analysis of covariance was used to compare the cell index values. Results: In comparison with the control group; oxyresveratrol 10 µM and melatonin 100 pM groups increased proliferation whereas oxyresveratrol 25 µM, oxyresveratrol 50 µM, and melatonin 100 µM groups induced cytotoxicity (P < .05). IC50 values at 24th, 48th, and 72th hours were 946 nM, 1220 nM, and 1243 nM for melatonin and 23 µM, 22.2 µM, and 22.5 µM for oxyresveratrol, respectively. Conclusion: Cytotoxicity of melatonin was higher than oxyresveratrol and they both increased dental pulp stem cells' proliferation at lower doses and induced cytotoxicity at higher doses. [ABSTRACT FROM AUTHOR]

Morus alba L. is used for a range of therapeutic purposes in Asian traditional medicine, and its extracts are reported to be effective against lipidemia, diabetes, and obesity, as well as being hepatoprotective and tyrosinase-inhibitory. They are also included in cosmetic products as anti-aging and skin-whitening agents. Stilbenes, the major bioactive compounds found in M. alba, have received renewed attention recently because of their putative activity against COVID-19. In this study M. alba plants were established in vitro, and the effect of elicitation on plant growth and stilbene accumulation, specifically oxyresveratrol and trans-resveratrol, was investigated. Different concentrations of the elicitors including methyl jasmonate and cyclodextrins were applied, and stilbene levels were determined in leaves, roots, and the culture medium. Elicitation of the M. alba plants with 5 mM cyclodextrins, alone or in combination with 10 µM methyl jasmonate, significantly increased the total phenolic content in the culture medium and leaves after 7 days of treatment. The higher total phenolic content in the roots of control plants and those treated only with methyl jasmonate indicated that cyclodextrins promoted metabolite release to the culture medium. Notably, the cyclodextrin-treated plants with the highest levels of oxy- and trans-resveratrol also had the highest total phenolic content and antioxidant capacity. These results indicate that elicited M. alba in vitro plants constitute a promising alternative source of bioactive stilbenes to supply pharmaceutical and cosmeceutical industries. [ABSTRACT FROM AUTHOR]

Oxyresveratrol (OXY) is a naturally occurring phenolic compound; however, there are no toxicity studies reported on its long term use. The aim of our work was to demonstrate the evaluation of acute and sub-chronic toxicity of oxyresveratrol in rats to assess its safety profile. To evaluate the LD50 value, 2000 mg/kg of oxyresveratrol was administered to Wistar rats by oral gavage. For sub-chronic toxicity assessment, 80 Wistar rats were randomly divided into four groups (10 animal/sex/group) and oxyresveratrol administered at a dose of 50, 100, 150 mg/kg/day by oral gavage. Bodyweight, food, and water consumption were monitored every week. At the end of the experiments, biochemical and hematological parameters were analyzed. Gross and microscopic organ analyses were also carried out. LD50 of oxyresveratrol was greater than 2000 mg/kg sub-chronic administration of oxyresveratrol did not influence any mortality. Doses of 50 and 100 mg/kg of oxyresveratrol did not produce any sign of toxicity. However, the 150 mg/kg oxyresveratrol group depicted changes in multiple biochemical and hematological parameters with changes in the pathology of cardiac, hepatic, and renal tissues when compared with control. Therefore, no observed adverse effect level (NOAEL) of oxyresveratrol was observed to be 100 mg/kg per day for both male and female rats. The very first study of oral chronic toxicological assessment of oxyresveratrol. Pathological alterations were noted in liver and kidney in 150 mg/kg B.W. per day (High Dose) groups for 90 days. No remarkable effects were recorded in Wistar rats for acute oral exposure (2 g/kg B.W.). The NOAEL for chronic toxicity of Oxyresveratrol was 100 mg/kg B.W. per day for rats when administered orally for 90 days. [ABSTRACT FROM AUTHOR]

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Plant natural products offer promise in combating multi-drug resistance by acting as antibacterial agents through various mechanisms. A metabolomic-guided phytochemical investigation, based on a LC-HRMS/MS and Molecular Networking combined approach, was carried out on an extract of M. alba L. (mulberry) twigs, a common of byproduct of mulberry utilization. Molecular Networking uncovered different clusters of prenylated polyphenols, glycosylated phenolic compounds, and Diels-Alder dimers, steering the phytochemical profiling of this extract. This led to the swift annotation and subsequent isolation of 17 secondary metabolites including stilbenoids, flavonoids, and flavanones. Isolated metabolites were tested for their antimicrobial activity against Staphylococcus species. The most active compound resulted to be kuwanon C, exhibiting a MIC value of 8 μg/mL against the methicillin resistant S. aureus (MRSA) strain and a biofilm producer strain of S. epidermidis. We also observed an interaction between 4 μg/mL of kuwanon C in combination with low oxacillin dosage against the MRSA. Thanks to the high chemical structure similarity of isolated metabolites, structure-activity relationships of these versatile scaffolds have been postulated. [Display omitted] [ABSTRACT FROM AUTHOR]

[Display omitted] • OXY has the ability to support the amelioration of post-inflammatory hyperpigmentation mechanisms. • OXY was purified from mulberry extract, a traditional Chinese medicine. • OXY effectively inhibited melanin synthesis in human melanocytes. • OXY significantly inhibited melanosome transfer to keratinocytes. • OXY can repair the barrier function and provide photoprotective properties in a UVB-induced keratinocyte damage model. Mulberry (Morus alba L.) twigs are a traditional Chinese medicine and edible agricultural by-product. Oxyresveratrol (OXY) is one of the natural resorcinol-type polyphenols obtained from mulberry twigs with anti-melanogenesis effects. This study aimed to investigate the ameliorative effects and mechanisms of OXY on post-inflammatory hyperpigmentation (PIH) in vitro. The results of DPPH radical scavenging and tyrosinase inhibition assays showed that OXY exhibited potent antioxidant and tyrosinase inhibitory activities. In human melanocytes, OXY significantly down-regulated protein expression related to melanin synthesis and transport. A molecular docking study suggested that OXY could inhibit these GTPases (RAB27A, RAC1, and CDC42) activities in melanosome transfer processes. Furthermore, OXY significantly reduced inflammatory factor secretion, promoted human β-defensin production, and up-regulated the expression of barrier proteins in UVB-induced human keratinocytes. This research indicated that the OXY from mulberry twigs has potential applications in ameliorating PIH through its antioxidant, anti-melanogenic, melanosome transport inhibition, anti-inflammatory, and photoprotective properties. [ABSTRACT FROM AUTHOR]

Oxyresveratrol (OXY), a natural stilbenoid in mulberry fruits, is known for its diverse pharmacological properties. However, its clinical use is hindered by low water solubility and limited bioavailability. In the present study, the inclusion complexes of OXY with β-cyclodextrin (βCD) and its three analogs, dimethyl-β-cyclodextrin (DMβCD), hydroxypropyl-β-cyclodextrin (HPβCD) and sulfobutylether-β-cyclodextrin (SBEβCD), were investigated using in silico and in vitro studies. Molecular docking revealed two binding orientations of OXY, namely, 4′,6′-dihydroxyphenyl (A-form) and 5,7-benzenediol ring (B-form). Molecular Dynamics simulations suggested the formation of inclusion complexes with βCDs through two distinct orientations, with OXY/SBEβCD exhibiting maximum atom contacts and the lowest solvent-exposed area in the hydrophobic cavity. These results corresponded well with the highest binding affinity observed in OXY/SBEβCD when assessed using the MM/GBSA method. Beyond traditional simulation methods, Ligand-binding Parallel Cascade Selection Molecular Dynamics method was employed to investigate how the drug enters and accommodates within the hydrophobic cavity. The in silico results aligned with stability constants: SBEβCD (2060 M−1), HPβCD (1860 M−1), DMβCD (1700 M−1), and βCD (1420 M−1). All complexes exhibited a 1:1 binding mode (A L type), with SBEβCD enhancing OXY solubility (25-fold). SEM micrographs, DSC thermograms, FT-IR and 1H NMR spectra confirm the inclusion complex formation, revealing novel surface morphologies, distinctive thermal behaviors, and new peaks. Notably, the inhibitory impact on the proliferation of breast cancer cell lines, MCF-7, exhibited by inclusion complexes particularly OXY/DMβCD, OXY/HPβCD, and OXY/SBEβCD were markedly superior compared to that of OXY alone. [Display omitted] • Investigation of inclusion complexes of OXY with βCD and analogs using in silico and in vitro studies. • Utilizing novel Parallel Cascade Selection Molecular Dynamics simulations for studying drug-cyclodextrin (CD) inclusion complexes. • Enhancing solubility and anticancer activity of OXY , especially OXY/SBEβCD showed superior inhibitory impact on MCF-7 cells compared to OXY alone. [ABSTRACT FROM AUTHOR]

Objectives: Resveratrol and oxyresveratrol, a resveratrol derivative, possess various pharmacological activities, including anti-cancer activities. Because cancer stem cells play an important role in cancer recurrence, the aims of this study were to investigate whether resveratrol or oxyresveratrol can inhibit the expression of cancer stem cell markers under hypoxia. Materials and methods: Deferoxamine was used to mimic the hypoxic condition. The mRNA expression of cancer stem cell markers was analyzed by Real-time PCR. Flow cytometry was used to determine the number of CD-44+ and CD-105+ cells. Results: Deferoxamine dose-dependently induced the expression of cancer stem cell markers; Oct-4, Nanog, CD-44, CD-105, and CD-133. The induction of these cancer stem cells markers was inhibited when the cells were treated with either resveratrol or oxyresveratrol. Moreover, we found that resveratrol also reduced the number of CD-44+ and CD-105+ cells after deferoxamine treatment. Conclusions: Resveratrol and oxyresveratrol inhibit the expression of cancer stem cell markers and might target cancer stem cells in a hypoxia-associated tumor.

Abstract The aim was to scrutinize the in vivo and in vitro activities against Leishmania tropica with compounds of Oxyresveratrol, Quercetin O-Hexoside, and Quercetin 3-Glucoside. The in vitro outcomes against Leishmania were analyzed for 24-48 hours on L. tropica KWH23 promastigotes with compounds materials having 50 - 200 µg/mL concentration with negative control and standard drug Amphotericin B. The compounds were analyzed in L. tropica infected BALB/c mice against Leishmania tropica. The Quercetin 3-Glucoside shows mean inhibition of extracellular promastigotes after 48 hours at 50, 100, 150, 200 µg/mL were 91.02 ± 0.12, 94.50 ± 0.07, 96.15 ± 0.17 and 97.01 ± 0.08 % respectively. In BALB/c mice, the intracellular amastigotes were 91% cured at 200 µg/mL and mean lesion size decreased to 0.41 ± 0.21 mm (p < 0.01). The result shows that Quercetin 3-Glucoside possesses significant anti-leishmanial activity.

Mulberry branch (Morus spp.) is an agricultural byproduct enriched with polyphenol and flavone. Mulberry branch extract has been reported to protect human umbilical vein endothelial cells (HUVECs) from oxidized low-density lipoprotein (ox-LDL) injury. However, the active ingredient derived from mulberry branch extract responsible for the protective action and the specific mechanism remain to be clarified. In the current study, the main active ingredient with anti-oxidant activity of mulberry branch extract was rapid-screened using the DPPH-HPLC method. Subsequently, the chemical structure was solved with mass spectrometry and nuclear magnetic resonance spectroscopy. Cell viability, levels of malondialdehyde (MDA) and superoxide dismutases (SODs) were measured to evaluate the protective action of the ingredient for HUVECs against ox-ldl-induced injury. DHE and DCFH-DA fluorescent probes were used to measure the level of intracellular reactive oxygen species (ROS). Real-time qPCR and Western blot were conducted to detect mRNA and protein levels. We found that the Oxyresveratrol was the main anti-oxidant ingredient that protecetd HUVECs against ox-ldl-induced injury. The protective action might be achieved via the up-regulation of the Nrf-2/HO-1 signaling and reduction of ROS production. Futhermore, the protective effect of Oxyresveratrol could be reversed by suppression of Nrf-2. Molecular docking analysis revealed strong binding between Oxyresveratrol and Keap-1/Nrf-2 protein complex, mainly via hydrogen bonds linking the specific amino acid residues on the target proteins. Molecular-dynamics simulation suggested that Oxyresveratrol led to dissociation of Nrf-2 from Keap-1 via binding to the Keap-1/Nrf-2 complex. In all, the current study showed that Oxyresveratrol, an active ingredient of mulberry branch extract, could protect HUVECs against the ox-ldl-induced oxidative injury via the dissociation of Nrf-2 from the Keap-1/Nrf-2 to axtivate the Nrf-2/HO-1 signaling pathway. Thus, the Oxyresveratrol might be potent in prevention and treatment of atherosclerosis.

Stilbenoids are well-known phytoalexins in the group of polyphenolic compounds. Because of their potent bioactivities, including antioxidant, antityrosinase, photoprotective, and antibacterial activities, stilbenoids are utilized as pharmaceutical active ingredient in cosmetic products. Thus, the demand for stilbenoids in the cosmetic industry is increasing. The main sources of stilbenoids are plants. Although plants are green and sustainable source materials, some of them do not allow a regular and constant supply due to seasonal and geographic reasons. Stilbenoids typically have been extracted by conventional organic solvent extraction, and then purified by separation techniques. This method is unfriendly to the environment and may deteriorate human health. Hence, the procedures called "green technologies" are focused on novel extraction methods and sustainable stilbenoids production by using biotechnology. In this review, the chemical structures together with the biosynthesis and current plant sources of resveratrol, oxyresveratrol, and piceatannol are described. Furthermore, recent natural deep eutectic solvents (NADES) for green extraction as well as plant cell cultures for the production of those stilbene compounds are updated. [ABSTRACT FROM AUTHOR]

The naturally occurring stilbenoid oxyresveratrol was shown to influence inflammatory and metabolic processes. During cellular immune activation, tryptophan breakdown and neopterin formation via the enzymes indoleamine 2,3-dioxygenase-1 (IDO-1) and GTP-cyclohydrolase, respectively, are induced. Neopterin and the kynurenine to tryptophan ratio are reliable and pertinent biomarkers of Th1-type immune response and are also used in vitro to monitor effects of active plant ingredients on peripheral blood mononuclear cells (PBMCs). We investigated the effects of oxyresveratrol on the activity of the above-mentioned pathways in mitogen-stimulated human PBMC and in the myelomonocytic cell line THP-1. Oxyresveratrol exerted suppressive effects on tryptophan breakdown in both stimulated cell models. Of note, in PBMC, tryptophan breakdown was induced at lower concentrations (5–20 µM) and suppressed at higher treatment concentrations only. Neopterin formation was decreased dose-dependently in stimulated PBMC. In unstimulated PBMC similar, albeit lesser effects were observed. Data indicate that oxyresveratrol exerts distinct and concentration-dependent effects on different immune cell types. IDO-1 is targeted by oxyresveratrol and its activity can be modulated in both directions. Detailed investigations of the interactions would be interesting to fully explore the activity of this phytocompound.

The work investigated the browning inhibition of oxyresveratrol (OXY) in fresh-cut potatoes by physicochemical and structural analysis. The results showed that the optimal inhibitory concentration was 0.002 % for fresh-cut potato sticks. Under this condition, oxyresveratrol inhibited the activities of polyphenol oxidase (PPO), peroxidase (POD), cinnamate-4-hydroxylase (C4H) and catalase (CAT), and decreased the content of chlorogenic acid and caffeic acid, but increased the contents of catechic acid and epicatechin in fresh-cut potatoes. Further analysis found that oxyresveratrol was a competitive inhibitor for PPO with the strong ability to chelate Cu2+. Oxyresveratrol formed hydrogen bonds with Ala246, Ala143, Met247 and Ala146 of StPPO2, and constructed stable hydrophobic interactions with His144, Pro245, Glu145 and Ile151 residues. The analysis of tertiary and secondary structures showed that oxyresveratrol decreased the fluorescence intensity and α-helix content of PPO, but increased β-sheet and β-turn content. The results showed that oxyresveratrol is a promising anti-browning agent for fresh-cut potatoes. • Oxyresveratrol (0.002 %) significantly inhibited browning of fresh-cut potato. • Oxyresveratrol inhibited PPO and CAT activities, and improved total phenol content. • Oxyresveratrol was competitive inhibitor for PPO with strong ability to chelate Cu2+. • Hydrogen bond and hydrophobic interaction was main force between oxyresveratrol (OXY) and PPO. • Oxyresveratrol decreased the fluorescence intensity and α-helix content of PPO. [ABSTRACT FROM AUTHOR]

Oxyresveratrol (ORV) is one of the novel antioxidants having been extensively studied in recent years. One of the main sources of ORV is Artocarpus lakoocha, which has been used in traditional medicine in Thailand for decades. However, the role of ORV in skin inflammation has not been clearly demonstrated. Therefore, we investigated the anti-inflammatory effects of ORV on dermatitis model. The effect of ORV was examined on human immortalized and primary skin cells exposed to bacterial components including peptidoglycan (PGN) and lipopolysaccharide (LPS) and 2,4-Dinitrochlorobenzene (DNCB)-induced dermatitis mouse model. PGN and LPS were used to induce inflammation on immortalized keratinocytes (HaCaT) and human epidermal keratinocytes (HEKa). We then performed MTT assay, Annexin V and PI assay, cell cycle analysis, real-time PCR, ELISA and Western blot in these in vitro models. H&E staining, immunohistochemistry (IHC) staining with CD3, CD4 and CD8 markers were used to evaluate the effects of ORV in in vivo model of skin inflammation using BALB/c mice. Pretreatment of HaCaT and HEKa cells with ORV inhibited pro-inflammatory cytokine production through inhibition of NF-κB pathway. In DNCB-induced dermatitis mouse model, ORV treatment reduced lesion severity, and skin thickness and numbers of CD3, CD4 and CD8 T cells in the sensitized skin of mice. In conclusion, it has been demonstrated that ORV treatment can ameliorate inflammation in the in vitro models of skin inflammation and in vivo models of dermatitis, suggesting a therapeutic potential of ORV for treatment of skin diseases particularly eczema.

Antioxidants given concurrently with chemotherapy offer an effective strategy for reducing the negative effects of the drug. One remaining obstacle to the use of doxorubicin (DOX) in chemotherapy is cardiotoxicity. Using vitamin E (Vit. E) as a reference standard, our study focuses on the potential preventive benefits of oxyresveratrol (ORES) and/or dapagliflozin (DAPA) against DOX-induced cardiac injury. Acute cardiotoxicity was noticed after a single intravenous injection of a male rat's tail vein with 10 mg/kg of DOX. Oral doses of ORES (80 mg/kg), DAPA (10 mg/kg), and Vit. E (1 g/kg) were given, respectively. Pretreatment of animals with Vit. E, ORES and/or DAPA revealed a considerable alleviation of heart damage, as evidenced by histopathological change mitigation and a notable drop in serum AST, LDH, CK, CK-MB, and cardiac contents of MDA and NO 2 −. Also, serum TAC, tissue GSH, and SOD showed substantial increases. Additionally, tissue caspase-3, serum IL-6, and TNF-α were considerably reduced. Moreover, a downregulation in cardiac gene expression of ATG-5, Keap-1, and NF-κB in addition to an upregulation of Bcl-2 gene expression and HO-1, Nrf-2, and PPAR-γ protein expression clearly appeared. Ultimately, ORES and/or DAPA have an optimistic preventive action against severe heart deterioration caused by DOX. [Display omitted] • The most often administered anthracycline antibiotic during chemotherapy is doxorubicin (DOX). • Acute cardiotoxicity is one of DOX's primary adverse effects. • Oxyresveratrol (ORES) and/or dapagliflozin (DAPA) have a number of biological and pharmacological activities. • Either ORES or DAPA inhibited the expression of TNF-α, IL-6, Keap-1, NF-κB, caspase-3, and ATG-5. • HO-1, Bcl-2, PPAR-γ, and Nrf-2 were all elevated by ORES and/or DAPA. [ABSTRACT FROM AUTHOR]

The white mulberry (Morus alba L.) is widely used as a medicinal plant in Asia. In this study, the bioactive compounds of ethanolic extracts of white mulberry leaves from the Sakon Nakhon and Buriram cultivars were evaluated. The ethanolic extracts of mulberry leaves from the Sakon Nakhon cultivar showed the highest total phenolic content of 49.68 mg GAE/g extract and antioxidant activities of 4.38 mg GAE/g extract, 4.53 mg TEAC/g extract, and 92.78 mg FeSO4/g extract using 2,2 diphenyl-1-picrylhydrazyl (DPPH), 2,20-azinobis-(3-ethylbenzothiazolin-6-sulfonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) assays, respectively. The resveratrol and oxyresveratrol compounds in mulberry leaves were also investigated by high-performance liquid chromatography (HPLC). The mulberry leaf extracts from the Sakon Nakhon and Buriram cultivars showed oxyresveratrol contents of 1.20 ± 0.04 mg/g extract and 0.39 ± 0.02 mg/g extract, respectively, whereas resveratrol was not detected. It was also found that the potent anti-inflammatory properties of mulberry leaf extracts and its compounds, resveratrol and oxyresveratrol, suppressed the LPS-stimulated inflammatory responses in RAW 264.7 macrophage cells by significantly reducing nitric oxide production in a concentration-dependent manner. These compounds further inhibited interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) production and suppressed the mRNA and protein expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) in LPS-stimulated RAW 264.7 macrophage cells. Therefore, it is established that mulberry leaf extract and its bioactive compounds contribute to its anti-inflammatory activity.

Oxyresveratrol (OXY) has been reported for its anti-inflammatory activity; however, the pharmaceutical applications of this compound are limited by its physicochemical properties and poor pharmacokinetic profiles. The use of an ester prodrug is a promising strategy to overcome these obstacles. In previous researches, several carboxylate esters of OXY were synthesized and oxyresveratrol tetraacetate (OXY-TAc) was reported to possess anti-melanogenic and anti-skin-aging properties. In this study, in addition to OXY-TAc, two novel ester prodrugs of OXY, oxyresveratrol tetrapropionate (OXY-TPr), and oxyresveratrol tetrabutyrate (OXY-TBu), were synthesized. Results from the Caco-2-permeation assay suggested that synthesized ester prodrugs can improve the membrane-permeation ability of OXY. The OXY-TAc exhibited the most significant profile, then this prodrug was chosen to observe anti-inflammatory activities with lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Our results showed that OXY-Tac significantly alleviated secretion of several pro-inflammatory mediators (nitric oxide (NO), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α)), mitigated expression of enzyme-regulated inflammation (inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2)), and suppressed the MAPK cascades. Interestingly, the observed anti-inflammatory activities of OXY-TAc were more remarkable than those of its parent compound OXY. Taken together, we demonstrated that OXY-TAc improved physicochemical and pharmacokinetic profiles and enhanced the pharmacological effects of OXY. Hence, the results in the present study would strongly support the clinical utilities of OXY-TAc for the treatment of inflammation-related disorders. [ABSTRACT FROM AUTHOR]

Objective: To determine the Anti hyperlipidemic effect of Oxyresveratrol and Zinc complex on Total Cholesterol in Hyperlipidemic rat Model. Study Design: Experimental study. Setting: Islamic International Medical College Rawalpindi. Period: Sep 2020 to Sep 2021. Material & Methods: In our study on high fat diet fed hyperlipidemic rats comparison of this standard drug with a novel compound oxyresveratrol was done. Forty rats were randomly divided into 4 groups, Group I was used as NC (Negative Control), group II Positive Control (PC), group III (OXY-Zn complex) and group IV SIM respectively. Groups III and IV were given orally 10 mg/kg body wt. OXY-Zn and SIM respectively. Terminal sampling was performed on day 57 for estimation of total cholesterol. Results: OXY-Zn complex showed significantly better control over total cholesterol compared with SIM. Total cholesterol of OXY treated group showed p < 0.001 like SIM treated group (p < 0.001). Conclusion: Our results showed that OXY-Zn complex is better than simvastatin because of its significantly positive effect on total cholesterol when compared with SIM. [ABSTRACT FROM AUTHOR]

Objective: Osteosarcoma is a malignant tumor with high metastatic properties that are associated with increased mortality and poor prognosis. Therefore, it is crucial to develop an effective treatment for metastatic osteosarcoma. Oxyresveratrol (ORES), derived from mulberry twigs and fruits, has antitumor effects. However, it remains unknown whether ORES inhibits osteosarcoma metastasis. In this study, we determined the inhibitory effect of ORES on osteosarcoma metastasis. Key Findings: ORES attenuated the migration of U2OS cells, dose-dependently increased E-cadherin expression, and reduced N-cadherin expression in U2OS cells, indicating that ORES can inhibit epithelial–mesenchymal transition (EMT) in osteosarcoma cells. Furthermore, ORES inhibited the expression of Twist, which is associated with the downregulation of STAT3 phosphorylation. IL-6-induced STAT3 phosphorylation rescues the inhibitory effect of ORES on U2OS metastasis. Summary: Our results indicate that ORES is a potential therapeutic agent for metastatic osteosarcoma. ORES inhibits osteosarcoma cell migration by reducing EMT formation. [ABSTRACT FROM AUTHOR]

Microbial dysbiosis in dental plaque contributes to the occurrence of dental caries, to which Streptococcus mutans is a major contributor. Lactobacillus casei can be used as probiotic therapy to treat caries by replacing S. mutans within the dental plaque. However, the effects of probiotic treatment are not always stable. Oxyresveratrol (ORV), a plant-derived polyphenol, displays opposite effects in that it inhibits cariogenic and promotes commensal bacteria. Thus, the objectives of this study are to investigate the effects of ORV on bacterial proportions in S. mutans-L. casei biofilm and to elucidate how ORV weakens the competitiveness of S. mutans. Quantitative real-time PCR confirms a decreased S. mutans-L. casei ratio in dual-species biofilm by action of ORV. The culture supernatant of L. casei after being incubated with ORV (ORVLC) is prepared to explore the joint action of ORV and L. casei. ORVLC displays the strongest anti-biofilm effect against S. mutans when compared with the effects of L. casei supernatant or ORV alone. As a result of this treatment, both exopolysaccharides and bacteria contents in the biofilm are greatly reduced. The biofilm is transformed from water-insoluble glucandominant to water-soluble glucan-dominant by ORVLC through the modulation of the glycometabolism-related genes of S. mutans. As for the interactions between ORV and L. casei, ORV promotes L. casei to produce acetic acid, which provides L. casei with a competitive advantage against S. mutans. Taken together, ORV may be very suitable as an adjuvant medicine for probiotic therapy in the control of dental caries. [ABSTRACT FROM AUTHOR]

Oxyresveratrol (ORes, trans-2,4,3′,5′-tetrahydroxy stilbene) naturally exists in mulberry, grapes, peanuts and other plants. It belongs to stilbene polyphenolic family and has an extra hydroxyl group at 2-position comparing with resveratrol (Res). Hence, ORes has stronger antioxidant activity than resveratrol. In present study, we employed a rat hepatic fibrosis model induced by carbon tetrachloride (CCl4) and administrated ORes via gavage feeding to study the protective effects and potential mechanisms of ORes against hepatic fibrosis. We demonstrated that rat liver oxidative damage induced by CCl4 was significantly alleviated after ORes feeding. Furthermore, the mRNA transcription levels of α-smooth muscle actinn (α-SMA), desmin, and two MMPs (MMP2 and MMP9) were reduced and the expression levels of transforming growth factor β1 (TGF-β1), p- small mother against decapen-taplegic protein (Smad)1/2 and p-extracellular signal-regulated kinases (ERK)1/2 in the liver tissue down-regulated dramatically. In a parallel study with Res, ORes showed more efficacious protective effect than Res against rat liver fibrosis, which is attributed to extended conjugation system due to the extra hydroxyl group at 2-position on ORes making it more electron-rich and susceptible to oxidation than Res. Therefore, dietary consumption of mulberry and other fruits containing ORes may be beneficial in the prevention of liver fibrosis.

Resveratrol and oxyresveratrol, a resveratrol derivative, possess various pharmacological activities, including anti-cancer activities. Because cancer stem cells play an important role in cancer recurrence, the aims of this study were to investigate whether resveratrol or oxyresveratrol can inhibit the expression of cancer stem cell markers under hypoxia. Deferoxamine was used to mimic the hypoxic condition. The mRNA expression of cancer stem cell markers was analyzed by Real-time PCR. Flow cytometry was used to determine the number of CD-44 + and CD-105 + cells. Deferoxamine dose-dependently induced the expression of cancer stem cell markers; Oct-4 , Nanog , CD-44 , CD-105, and CD-133. The induction of these cancer stem cells markers was inhibited when the cells were treated with either resveratrol or oxyresveratrol. Moreover, we found that resveratrol also reduced the number of CD-44 + and CD-105 + cells after deferoxamine treatment. Resveratrol and oxyresveratrol inhibit the expression of cancer stem cell markers and might target cancer stem cells in a hypoxia-associated tumor. • Deferoxamine induced the expression of cancer stem cell markers. • Resveratrol and Oxyresveratrol suppressed deferoxamine-induced cancer stem cell marker expression. • Resveratrol reduced the number of CD-44 and CD-105 + cells after deferoxamine treatment. [ABSTRACT FROM AUTHOR]