Exploring Sorbus torminalis Leaves: Unveiling a Promising Natural Resource for Diverse Chemical and Biological Applications.

Sorbus torminalis (L.) Crantz has a rich history of versatile applications spanning the fields of medicine and nutrition. It is noteworthy that the decoction obtained from S. torminalis leaves is a traditional treatment method against both diabetes and stomach disorders. Phytochemical profiling determined by HPLC/MS-MS. The effects of the extracts on cell viability were investigated using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) method against MDA-MB-231 cell line (human breast adenocarcinoma).The ethanol/water extract contained more concentration of total phenolic (91.41 mg gallic acid (GAE) equivalent /gr) and flavanoid (29.10 mg rutin (RE) equivalent/gr) in the tested extract (p<0.05). Resulting of HPLC analysis, the chemical constituents varied depending on the solvents and chlorogenic acid, hyperoside, isoquercetin, delphindin-3,5-diglucoside, procyanidin B2, epicatechin, neochlorogenic acid, 3,5-dicaffeoylquinic acid were identified in all extracts. Overall, ethanol, n-hexane and ethyl acetate extracts showed the highest inhibition for the tyrosinase enzyme. The effect of leaf extracts of S. torminalis on antimicrobial, biofilm inhibitory, and anticancer activities was examined. Based on outcomes of our study recognize this plant as a critical source of medically active chemicals for feasible phytopharmaceutical and nutraceutical applications, providing the first scientific insight into the detailed biological and chemical profiles of S. torminalis.

Morin ameliorates methotrexate-induced hepatotoxicity via targeting Nrf2/HO-1 and Bax/Bcl2/Caspase-3 signaling pathways.

BACKGROUND: Organ toxicity limits the therapeutic efficacy of methotrexate (MTX), an anti-metabolite therapeutic that is frequently used as an anti-cancer and immunosuppressive medicine. Hepatocellular toxicity is among the most severe side effects of long-term MTX use. The present study unveils new confirmations as regards the remedial effects of morin on MTX-induced hepatocellular injury through regulation of oxidative stress, apoptosis and MAPK signaling. METHODS AND RESULTS: Rats were subjected to oral treatment of morin (50 and 100 mg/kg body weight) for 10 days. Hepatotoxicity was induced by single intraperitoneal injection of MTX (20 mg/kg body weight) on the 5th day. MTX related hepatic injury was associated with increased MDA while decreased GSH levels, the activities of endogen antioxidants (glutathione peroxidase, superoxide dismutase and catalase) and mRNA levels of HO-1 and Nrf2 in the hepatic tissue. MTX treatment also resulted in apoptosis in the liver tissue via increasing mRNA transcript levels of Bax, caspase-3, Apaf-1 and downregulation of Bcl-2. Conversely, treatment with morin at different doses (50 and 100 mg/kg) considerably mitigated MTX-induced oxidative stress and apoptosis in the liver tissue. Morin also mitigated MTX-induced increases of ALT, ALP and AST levels, downregulated mRNA expressions of matrix metalloproteinases (MMP-2 and MMP-9), MAPK14 and MAPK15, JNK, Akt2 and FOXO1 genes. CONCLUSION: According to the findings of this study, morin may be a potential way to shield the liver tissue from the oxidative damage and apoptosis.

Hesperidin Attenuates Oxidative Stress, Inflammation, Apoptosis, and Cardiac Dysfunction in Sodium Fluoride-Induced Cardiotoxicity in Rats.

Excessive fluoride intake has been reported to cause toxicities to brain, thyroid, kidney, liver and testis tissues. Hesperidin (HSP) is an antioxidant that possesses anti-allergenic, anti-carcinogenic, anti-oxidant and anti-inflammatory activities. Presently, the studies focusing on the toxic effects of sodium fluoride (NaF) on heart tissue at biochemical and molecular level are limited. This study was designed to evaluate the ameliorative effects of HSP on toxicity of NaF on the heart of rats in vivo by observing the alterations in oxidative injury markers (MDA, SOD, CAT, GPX and GSH), pro-inflammatory markers (NF-κB, IL-1ß, TNF-α), expressions of apoptotic genes (caspase-3, -6, -9, Bax, Bcl-2, p53, cytochrome c), levels of autophagic markers (Beclin 1, LC3A, LC3B), expression levels of PI3K/Akt/mTOR and cardiac markers. HSP treatment attenuated the NaF-induced heart tissue injury by increasing activities of SOD, CAT and GPx and levels of GSH, and suppressing lipid peroxidation. In addition, HSP reversed the changes in expression of apoptotic (caspase-3, -6, -9, Bax, Bcl-2, p53, cytochrome c), levels of autophagic and inflammatory parameters (Beclin 1, LC3A, LC3B, NF-κB, IL-1ß, TNF-α), in the NaF-induced cardiotoxicity. HSP also modulated the gene expression levels of PI3K/Akt/mTOR signaling pathway and levels of cardiac markers (LDH, CK-MB). Overall, these findings reveal that HSP treatment can be used for the treatment of NaF-induced cardiotoxicity.

Hesperidin protects liver and kidney against sodium fluoride-induced toxicity through anti-apoptotic and anti-autophagic mechanisms.

AIM: High dose of fluoride intake is associated with toxic effects on liver and kidney tissues. One approach to tackle these toxicities is using natural antioxidants as supplements. This study evaluated the ameliorative effects of hesperidin (HSP) against sodium fluoride (NaF)-induced hepatotoxicity and nephrotoxicity in wistar albino rats. MATERIALS AND METHODS: In the present study, the rats were randomly allocated into five groups of seven male rats each group: control, NaF (600 ppm), HSP-200, NaF + HSP-100 and NaF + HSP 200. KEY FINDINGS: Hepatic and renal injuries induced by NaF were confirmed by the alteration in kidney function parameters in the serum (urea and creatinine), levels of liver enzymes (ALT, ALP and AST), activities of the antioxidant enzymes (SOD, CAT and GPx) and levels of inflammatory markers (NF-κB, IL-1ß and TNF-α). NaF also inhibited PI3K/Akt/mTOR pathway, increased levels of autophagic markers (Beclin-1, LC3A and LC3B) and expression levels of apoptotic and anti-apoptotic proteins (Bax, Bcl-2, cytochrome c, p53 and procaspase-3) in the liver and kidney tissues. Administration of HSP concurrently with NaF significantly ameliorated the deviation in the above-studied parameters. SIGNIFICANCE: The results of the current study revealed that HSP could be used as a beneficial adjuvant that confers protection against NaF-induced liver and kidney damage through antioxidant, anti-inflammatory, anti-apoptotic and anti-autophagic mechanisms.

Morin protects against acrylamide-induced neurotoxicity in rats: an investigation into different signal pathways.

The presented study investigates the effects of morin against toxicity induced by acrylamide (ACR) in the brains of Sprague Dawley rats. In this study, neurotoxicity was induced by orally administering 38.27 mg/kg/b.w ACR to rats through gastric gavage for 10 days. Morin was administered at the same time and at different doses (50 and 100 mg/kg/b.w) with ACR. Biochemical and Western blot analyses showed that ACR increased malondialdehyde (MDA), p38α mitogen-activated protein kinase (p38α MAPK), nuclear factor kappa-B (NF-κB), tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1ß), interleukin-6 (IL-6), cyclooxygenase-2 (COX-2), p53, caspase-3, bcl-2 associated X protein (Bax), Beclin-1, light chain 3A (LC3A), and light chain 3B (LC3B) levels and decreased those of superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione (GSH), b-cell lymphoma-2 (Bcl-2), mammalian target of rapamycin (mTOR), phosphoinositide 3-kinase (PI3K), and protein kinase B (Akt) in brain tissue and therefore induced neurotoxicity by causing oxidative stress, inflammation, apoptosis, and autophagy. On the other hand, it was determined that morin positively affected the levels of these markers by displaying antioxidant, anti-inflammatory, anti-apoptotic, and anti-autophagic properties and had a protective effect on ACR-induced neurotoxicity. As a result, morin is an effective substance against brain damage caused by ACR, yet further studies are needed to use it effectively.

Modulatory effects of carvacrol against cadmium-induced hepatotoxicity and nephrotoxicity by molecular targeting regulation.

AIM: Cadmium (Cd) is a toxic heavy metal that causes severe toxic effects on different tissues including liver and kidney. Therefore the research for alternatives to reduce the damage caused by Cd has substantial importance. This study was performed to examine the possible modulatory effects of carvacrol (CRV) against Cd-induced hepatorenal toxicities and the possible mechanisms underlying these effects. MATERIALS AND METHODS: In the present study, 35 male Wistar rats were randomly divided into 5 groups. The rats were treated with Cd (25 mg/kg) and treated with CRV (25 and 50 mg/kg body weight) for 7 consecutive days. KEY FINDINGS: CRV could modulate Cd-induced elevations of ALT, ALP, AST, urea, creatinine, MDA and enhance antioxidant enzymes' activities such as SOD, CAT, and GPx, and GSH's level. CRV also reversed the changes in levels of inflammatory biomarker and apoptotic genes that include NF-κB, Bcl-3, MAPK-14, iNOS, COX-2, MPO, PGE2, Bax, Bcl-2, P53, Caspase-9, Caspase-6 and Caspase-3 in both tissues. The levels of 8-OHdG in the Cd-induced liver and kidney tissues were modulated after CRV treatment. Furthermore, CRV treatment considerably lowered Cd, Na, Fe, and Zn content while increased K, Ca, Mg and Cu contents in both tissues as compared to the Cd-exposed rats. SIGNIFICANCE: The results of the present study revealed that CRV supplementation could be a promising strategy to protect the liver and kidney tissues against Cd-induced oxidative damage, inflammation and apoptosis.

Quercetin, chrysin, caffeic acid and ferulic acid ameliorate cyclophosphamide-induced toxicities in SH-SY5Y cells.

Clinical use of cyclophosphamide (CP) causes apoptosis-induced cell death in the immune system, liver, heart and kidneys. To prevent the cells against side effects of CP and its metabolites, increasing antioxidant defence mechanism of the body with supplemental antioxidants is important. Therefore, there is a requirement for effective agents which could prevent the healthy cells from the harmful effects of drug-induced toxicities. Several antioxidants have been used in protecting or alleviating CP-induced cell death. However, no such study is reported in CP-induced SH-SY5Y cell toxicity. The aim of this study was to evaluate likelihood ameliorative effects of caffeic acid, chrysin, quercetin and ferulic acid against CP-induced toxicity in SH-SY5Y neuron cells. In this study protective effects of quercetin, chrysin, caffeic acid and ferulic acid against CP-induced cell toxicity in SH-SY5Y cells was evaluated by cell proliferation assay, lipid peroxidation (LPO) analysis to decipher antioxidant capacity, tunel assay and qRT-PCR experiments to examine anti-apoptotic activities of the antioxidants. The results showed that CP-induced cell toxicity in SH-SY5Y cells and treatments with the antioxidants suppressed the cell death. Our results suggests that these anti-oxidants protected SH-SY5Y cells via a decrease in LPO levels, downregulating the expression of Cas-3, Cyt c and Bax and upregulating expression of anti-apoptotic gene Bcl-2. The use of antioxidant as nutritional supplements, and in particular of caffeic acid, chrysin, quercetin and ferulic acid, reduce apoptotic effects of CP in SH-SY5Y cells that could add insight into therapeutic approaches to CP-induced cell injuries.

Zingerone attenuates vancomycin-induced hepatotoxicity in rats through regulation of oxidative stress, inflammation and apoptosis.

AIM: Vancomycin (VCM) is a glycopeptide antibiotic widely used to treat serious infections caused by methicillin-resistant Staphylococcus aureus and has been associated with some severe side effects such as hepatotoxicity and nephrotoxicity. However, the underlying mechanism of VCM-induced hepatotoxicity is not yet fully understood. Therefore, the current study was designed to evaluate the protective effects of zingerone (Zin) against VCM-induced hepatotoxicity in rats. MATERIALS AND METHODS: VCM was intraperitoneally administered at a dose of 200 mg/kg body weight (b.w.) for 7 days alone and in combination with the orally administered Zin (25 and 50 mg/kg b.w). KEY FINDINGS: Zin treatment significantly improved VCM-induced hepatic lipid peroxidation, glutathione depletion, reduced antioxidant enzyme (superoxide dismutase, catalase and glutathione peroxidase) activities and liver function markers (aspartate aminotransferase, alkaline phosphatase and alanine aminotransferase). Histopathological integrity and immunohistochemical expression of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the VCM-induced liver tissue were ameliorated after Zin administration. In addition, Zin reversed the changes in levels and/or activities of inflammatory and apoptotic parameters such as nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), p53, cysteine aspartate specific protease-3 (caspase-3), cysteine aspartate specific protease-8 (caspase-8), cytochrome c, Bcl-2 associated X protein (Bax) and B-cell lymphoma-2 (Bcl-2) in the VCM-induced hepatotoxicity. SIGNIFICANCE: Collectively, these results reveal probable ameliorative role of Zin against VCM-induced hepatotoxicity.

Morin attenuates acrylamide-induced testicular toxicity in rats by regulating the NF-κB, Bax/Bcl-2 and PI3K/Akt/mTOR signaling pathways.

AIM: Acrylamide (AC) is a carcinogenic substance which is formed during the heating of starchy foods at high temperatures and constitutes an important risk for human health. Therefore, reducing the detrimental effects of AC has become an important research topic. This study was performed to evaluate the protective effect of morin against the testicular toxicity induced by AC in male rats. MATERIALS AND METHODS: Testicular damage was evaluated after the rats were treated orally with AC (38.27 mg/kg body weight) alone or with morin (50 and 100 mg/kg body weight) for 10 consecutive days. KEY FINDINGS: Our results showed that treatment with morin could significantly decrease MDA level and considerably increase the activity of antioxidant enzymes (SOD, CAT, GPx) and GSH level in the testicular tissue of the AC-treated rats. Morin supplementation also suppressed the activation of inflammatory, apoptotic and autophagic pathways by increasing Bcl-2 and decreasing p38α MAPK, TNF-α, NF-κB, IL-1ß, IL-6, COX-2, cytochrome c, Bax, caspase-3, LC3A, LC3B and beclin-1 protein levels. Morin also alleviated the side effects caused by AC by regulating the PI3K/Akt/mTOR signaling pathway. SIGNIFICANCE: Collectively, our results have shown the possible protective mechanism of morin, a potential therapeutic agent for AC-induced testicular toxicity.

Melatonin and vitamin E alleviate homocysteine-induced oxidative injury and apoptosis in endothelial cells.

A relationship exists between hyperhomocysteinemia and cardiovascular diseases, although the underlying mechanisms are still incompletely defined. One possibility involves a homocysteine (Hcy)-induced increased oxidative stress. Melatonin (Mel) and vitamin E (vitE) are important anti-oxidants. The main purpose of this study was (1) to compare the effect of treatments with Mel, vitE or both, on Hcy-induced apoptosis in human umbilical vein endothelial cells (HUVECs), and (2) to investigate the underlying mechanisms. Cell proliferation assay was carried out by Water Soluble Tetrazolium-1 (WST-1) assay kit. Apoptotic index was calculated by TUNEL Assay. Anti-oxidant parameters were studied by measurement of reactive oxygen species (ROS) and lipid peroxidation (LPO) levels. mRNA and protein expression levels of apoptotic and anti-apoptotic genes and proteins were studied by quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting experiments respectively. The results showed that treatments with Mel, vitE or Mel + vitE suppressed Hcy-induced cell death, with a higher efficiency for the Mel and Mel + vitE treatments. Our results suggests that the mechanisms by which these anti-oxidants protected endothelial cells include the decrease in ROS and LPO levels, an increase in cell migration, the downregulation of pro-apoptotic proteins Cas 3, Cas 9, Cyt C and Bax and the upregulation of anti-apoptotic protein Bcl 2. Collectively, these results revealed the protective role of vitE and Mel against Hcy-induced cell apoptosis, which may add insight into therapeutic approaches to Hcy-induced damages.

Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: A multi-biomarker approach.

Acrylamide (ACR) is a heat-induced carcinogen substance that is found in some foods due to cooking or other thermal processes. The aim of present study was to assess the probable protective effects of morin against ACR-induced hepatorenal toxicity in rats. The rats were treated with ACR (38.27 mg/kg b.w., p.o.) alone or with morin (50 and 100 mg/kg b.w., p.o.) for 10 consecutive days. Morin treatment attenuated the ACR-induced liver and kidney tissue injury by diminishing the serum AST, ALP, ALT, urea and creatinine levels. Morin increased activities of SOD, CAT and GPx and levels of GSH, and suppressed lipid peroxidation in ACR induced tissues. Histopathological changes and immunohistochemical expressions of p53, EGFR, nephrin and AQP2 in the ACR-induced liver and kidney tissues were decreased after administration of morin. In addition, morin reversed the changes in levels of apoptotic, autophagic and inflammatory parameters such as caspase-3, bax, bcl-2, cytochrome c, beclin-1, LC3A, LC3B, p38α MAPK, NF-κB, IL-1ß, IL-6, TNF-α and COX-2 in the ACR-induced toxicity. Morin also affected the protein levels by regulating the PI3K/Akt/mTOR signaling pathway and thus alleviated ACR-induced apoptosis and autophagy. Overall, these findings may shed some lights on new approaches for the treatment of ACR-induced hepatotoxicity and nephrotoxicity.

Neuroprotective Effects of Chrysin on Diclofenac-Induced Apoptosis in SH-SY5Y Cells.

Accumulating evidences demonstrated that Reactive Oxygen Species (ROS) may lead to serious damages to numerous cellular biomolecules, consequently resulting in the development of several neurological diseases. Diclofenac (Dic), the most widely preferred non-steroidal anti-inflammatory drug (NSAID) induces apoptosis by an alteration in function of mitochondria and creation of ROS. Chrysin (Chr) is a naturally active component that is found in numerous plants and bee products and retains strong neuroprotective and antioxidant properties. However its effect of Dic induced injury on SH-SY5Y neuron cells have not been investigated to date. The goal of present research was to study the molecular mechanisms of Chr protection from oxidative injury caused by Dic in SH-SY5Y cells. Dic induced significant toxicity on the cells and this effect was reversed by pre-treatment with Chr. Dic triggered a noteworthy increase in the cellular ROS and Lipid peroxidation (LPO) levels and decrease in Total antioxidant status (TAS) level while pre-treatment with Chr reversed these effects. Dic induction increased the Bax, cytochrome c, cas-3, cas-8 and p53 expression at gene transcription level. Elevated levels of these genes considerably decreased by Chr pre-treatment revealing the defensive effects of Chr. The results obviously presented that exposure of SH-SY5Y with Dic resulted in oxidative stress and apoptosis while pre-treatment of neuron cells with Chr protects the cells against apoptosis triggered by Dic induction.

Rutin ameliorates mercuric chloride-induced hepatotoxicity in rats via interfering with oxidative stress, inflammation and apoptosis.

OBJECTIVE: Mercury is a global environmental pollutant and is responsible for several organ pathophysiology including oxidative stress-induced liver disorders. Therefore, the present study was conducted to evaluate the potential ameliorative effects of rutin on mercury chloride (HgCl2)-induced hepatotoxicity in adult male rats. METHODS: HgCl2 was intraperitoneally injected at a dose of 1.23 mg/kg body weight for 7 days alone or in combination with the orally rutin (50 and 100 mg/kg body weight). RESULTS: Rutin treatment significantly improved liver function tests [alkaline phosphatase (ALP), aspartate aminotransferase (AST) and alanine aminotransferase (ALT)], and increased activities of antioxidant defense system [catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx)] and glutathione (GSH) content. The histological alterations and epidermal growth factor receptor (EGFR) expression in the HgCl2-induced liver tissues were decreased by administration of rutin. Furthermore, rutin reversed the changes in levels of apoptosis and inflammation related proteins involving p53, Bcl-2 associated X protein (Bax), B-cell lymphoma-2 (Bcl-2), cytochrome c, nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), B-cell lymphoma-3(Bcl-3) and interleukin-1ß (IL-1ß), and inhibited p38α mitogen-activated protein kinase (MAPK) and cysteine aspartate specific protease-3 (caspase-3) activations. CONCLUSION: The data of the present study suggest that rutin effectively suppress HgCl2-induced hepatotoxicity by ameliorating oxidative stress, inflammation and apoptosis.

Turkish propolis supresses MCF-7 cell death induced by homocysteine.

Elevated plasma homocysteine (Hcy) level is a most important risk factor for various vascular diseases including coronary, cerebral and peripheral arterial and venous thrombosis. Propolis is produced by honeybee from various oils, pollens and wax materials. Therefore, it has various biological properties including antioxidant, antitumor and antimicrobial activities. This study investigated the effects of propolis and Hcy on apoptosis in cancer cells. According to our findings, Hcy induced apoptosis in human breast adenocarcinoma (MCF-7) cells by regulating numerous genes and proteins involved in the apoptotic signal transduction pathway. In contrast, treatment with propolis inhibited caspase- 3 and -9 induced by Hcy in MCF-7 cells. It can be concluded that Hcy may augment the activity of anticancer agents that induce excessive reactive oxygen species (ROS) generation and apoptosis in their target cells. In contrast to the previous studies herein we found that propolis in low doses protected cancer cells inhibiting cellular apoptosis mediated by intracellular ROS-dependent mitochondrial pathway.