Dose-Dependent Variation in Anticancer Activity of Hexane and Chloroform Extracts of Field Horsetail Plant on Human Hepatocarcinoma Cells.

Horsetail fern plant is botanically known as Equisetum arvense L., and it is a good source of phenolic flavonoids, phenolic acids, and compounds. Anticancer properties of hexane and chloroform extracts of the horsetail fern plant and their mechanisms involved in the anticancer activity on human hepatocarcinoma (HuH-7) cells were examined. Cytotoxicity was evaluated by using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) and NRU (neutral red uptake) assays. Other parameters such as oxidative stress and apoptosis in pretreated hexane and chloroform extracts of the horsetail fern plant were examined in HuH-7 cells. The observation showed that hexane and chloroform extract of the horsetail fern plant exhibited cytotoxicity against HuH-7 cells. The value of IC50-24 h of hexane and chloroform extract of the horsetail fern plant was determined as 199.0 µg/ml and 161.90 0 µg/ml for HuH-7 cells, respectively, and on the basis of IC50 value, three acute concentrations, viz., 75% of IC50, 50% of IC50, and 25% of IC50, were determined for further study. The lower dose of extracts hexane and chloroform extract of the horsetail fern plant did not show significant toxicity. Higher concentrations of extract induced significant antioxidant effects as well as apoptosis effects. However, exposure to hexane and chloroform extract of the horsetail fern plant upregulated the expression of Bax and p53 in HuH-7 cells. These data suggest that hexane and chloroform extract of the horsetail fern plant plays a significant role in the induction of toxicity via the regulation of oxidative stress in HuH-7 cells. This work may be useful for cancer chemotherapy.

Ameliorative effect of Spirulina and Saccharomyces cerevisiae against fipronil toxicity in Oreochromis niloticus.

The ameliorative effects of Spirulina and Saccharomyces cerevisiae (S. cerevisiae) against fipronil toxicity in Nile tilapia fish were investigated. Fipronil is a kind of pesticide that is widely used in agriculture, thus this trial was conducted to evaluate the effect of fipronil on growth related parameters (final body weight, feed intake, weight gain, feed conversion ratio, specific growth rate, and protein efficiency ratio), hematology related parameters (RBCs, WBCs, hemoglobin, packed cell volume, and deferential leukocytic count), biochemistry related parameters (alanine aminotransferase, aspartate aminotransferase, total protein, albumin, urea, and creatinine), histopathology of liver, intestine, gills, and spleen, and gene expression of antioxidants, stress, inflammatory, apoptotic, and related to junction proteins genes as SOD and GPx, COX II, TNF-α, Casp-3, and Claudin-3, respectively, in Nile tilapia (Oreochromis niloticus). Four hundred and five Nile tilapia fish were distributed in a glass aquarium into nine groups according to the Spirulina and S. cerevisiae supplemented diets, with or without fipronil contaminated water. The classified groups are control, Sc: S. cerevisiae (4 g/Kg diet), Sp: Spirulina (1 g/100 g diet), Fb1: 0.0021 mg fipronil/L, ScFb1: S. cerevisiae (4 g/Kg diet) with 0.0021 mg fipronil/L, SpFb1: Spirulina (1 g/100 g diet) with 0.0021 mg fipronil/L, Fb2: 0.0042 mg fipronil/L, ScFb2: S. cerevisiae (4 g/Kg diet) with 0.0042 mg fipronil/L, and SpFb2: Spirulina (1 g/100 g diet) with 0.0042 mg fipronil/L. The results of the present investigation indicated the negative effect of fipronil on the growth performance parameters of Nile tilapia, which was confirmed by the results of hematology, biochemistry, and histopathology. In addition, the results of gene expression of antioxidants, stress, inflammatory, and apoptotic genes indicate the genotoxicity of fipronil. However, these negative effects were ameliorated by Spirulina and Saccharomyces dietary supplementation.

Application of Green Technologies in Design-Based Extraction of Celastrus paniculatus (Jyotishmati) Seeds, SEM, GC-MS Analysis, and Evaluation for Memory Enhancing Potential.

Background: The Celastrus paniculatus (CP), commonly known as Jyotishmati, is considered as "elixir of life" by Indian people for the prevention or management of many ailments. The seed powder and its extract have widely used commercially for the preparation of various Ayurvedic formulations for the improvement of memory. CP seeds were generally extracted by conventional extraction methods (CEMs) which are assumed to impact environment burden and also produce low extract yield. Green extraction with possible improvement in extract yield has always been the need of hour for selected medicinal plant. Objective: In the present research, we aimed to optimize the different extraction factors in microwave and ultrasound-based extraction. The various extracts obtained in conventional and green methods are also evaluated for the possible improvement in memory enhancing potential. Materials and Methods: The selected medicinal herb was extracted by CEM (maceration and percolation). In green methods such microwave-assisted extraction (MAE) and ultrasound assisted-extraction (UAE), various parameters were optimized using Box-Behnken design coupled with response surface methodology. The scanning electron microscopy (SEM) and gas chromatography-mass spectroscopy (GC-MS) analyses were also done to confirm the possible improvement in concentration of plant actives. The Swiss albino mice were used to evaluate memory enhancing potential of different extracts. Results: At the optimized conditions MAE and UAE the extraction yield, total phenolic content (TPC) and Total flavonoid content (TFC) are significantly improved. The GC-MS analysis further confirms the improvement in concentration of certain fatty acid esters, pilocarpine, and steroidal compounds in optimized extracts. The optimized extracts also exhibited the significant improvement in behavioral parameters, oxidative stress-induced parameters, and acetylcholinesterase inhibitory potential. Discussion and Conclusion: From the results, we can say that the application of green technologies in design-based extraction of selected herb not only significantly reduces the extraction time but also improves the extract yield and concentration of plant actives. In nutshell, it can be concluded that the green approaches for extraction of seeds of Celastrus paniculatus could be scale up at a commercial level to meet the rising demand for herbal extract.

Potential of green-synthesized selenium nanoparticles using apigenin in human breast cancer MCF-7 cells.

The utilization of novel compounds as cancer treatments offers enormous potential in this field. The advantages of nanomedicine-based therapy include efficient cellular uptake and selective cell targeting. In this study, we employ selenium nanoparticles' green-synthesized by apigenin (SeNPs-apigenin) to treat breast cancer. We used various assays to show that SeNPs-apigenin can reduce MCF-7 cell viability and trigger apoptosis in vitro. Flow cytometry and PCR methods were used to detect apoptosis, while cell migration and invasion methods were used to quantify the possible effect of SeNPs-apigenin therapy on cell migration and invasion. According to cytotoxicity testing, the SeNPs-apigenin treatment can successfully limit MCF-7 cell proliferation and viability in a concentration-dependent manner. Flow cytometric and PCR analyses revealed that SeNPs-apigenin treatment induced apoptosis in MCF-7 cells, demonstrating that SeNPs-apigenin treatment could directly target Bcl-2, Bax, and caspase-3 and result in the discharge of cytochrome C from mitochondria into the cytosol, accompanied by the initiation of cell death, leading to permanent DNA damage and killing of MCF-7 cells. Furthermore, treatment with SeNPs-apigenin increased reactive oxygen species production and oxidative stress in MCF-7 cells. Our findings indicate that SeNPs-apigenin has cytotoxic potential in the treatment of breast cancer.

In-silico screening of naturally derived phytochemicals against SARS-CoV Main protease.

Coronavirus disease 2019 (COVID-19) is a rapidly growing pandemic that requires urgent therapeutic intervention. Finding potential anti COVID-19 drugs aside from approved vaccines is progressively going on. The chemically diverse natural products represent valuable sources for drug leads. In this study, we aimed to find out safe and effective COVID-19 protease inhibitors from a library of natural products which share the main nucleus/skeleton of FDA-approved drugs that were employed in COVID-19 treatment guidelines or repurposed by previous studies. Our library was subjected to virtual screening against SARS-CoV Main protease (Mpro) using Molecular Operating Environment (MOE) software. Twenty-two out of those natural candidates showed higher binding scores compared to their analogues. We repurpose these natural products including alkaloids, glucosinolates, and phenolics as potential platforms for the development of anti-SARS-CoV-2 therapeutics. This study paves the way towards discovering a lead used in the treatment of COVID-19 from natural sources and introduces phytomedicines with dual therapeutic effects against COVID-19 besides their original pharmacological effects. We recommend further in vitro evaluation of their anti-COVID-19 activity and future clinical studies.

Ziziphus spina-christi Leaf Extract Mitigates Mercuric Chloride-induced Cortical Damage in Rats.

BACKGROUND: Mercuric chloride (HgCl2) severely impairs the central nervous system when humans are exposed to it. AIMS: We investigated the neuroprotective efficiency of Ziziphus spina-christi leaf extract (ZSCLE) on HgCl2-mediated cortical deficits. METHODS: Twenty-eight rats were distributed equally into four groups: the control, ZSCLE-treated (300 mg/kg), HgCl2-treated (0.4 mg/kg), and ZSCLE+HgCl2-treated groups. Animals received their treatments for 28 days. RESULTS: Supplementation with ZSCLE after HgCl2 exposure prevented the deposition of mercury in the cortical slices. It also lowered malondialdehyde levels and nitrite and nitrate formation, elevated glutathione levels, activated its associated-antioxidant enzymes, glutathione reductase, and glutathione peroxidase, and upregulated the transcription of catalase and superoxide dismutase and their activities were accordingly increased. Moreover, ZSCLE activated the expression of nuclear factor erythroid 2-related factor 2 and heme oxygenase-1 when compared with the HgCl2 group. Notably, post-treatment with ZSCLE increased the activity of acetylcholinesterase and ameliorated the histopathological changes associated with HgCl2 exposure. Furthermore, ZSCLE blocked cortical inflammation, as observed by the lowered mRNA expression and protein levels of interleukin-1 beta and tumor necrosis factor-alpha, as well as decreased mRNA expression of inducible nitric oxide synthase. In addition, ZSCLE decreased neuron loss by preventing apoptosis in the cortical tissue upon HgCl2 intoxication. CONCLUSION: Based on the obtained findings, we suggest that ZSCLE supplementation could be applied as a neuroprotective agent to decrease neuron damage following HgCl2 toxicity.

GC-MS Analysis and Biomedical Therapy of Oil from n-Hexane Fraction of Scutellaria edelbergii Rech. f.: In Vitro, In Vivo, and In Silico Approach.

The current study aimed to explore the crude oils obtained from the n-hexane fraction of Scutellaria edelbergii and further analyzed, for the first time, for their chemical composition, in vitro antibacterial, antifungal, antioxidant, antidiabetic, and in vivo anti-inflammatory, and analgesic activities. For the phytochemical composition, the oils proceeded to gas chromatography-mass spectrometry (GC-MS) analysis and from the resultant chromatogram, 42 bioactive constituents were identified. Among them, the major components were linoleic acid ethyl ester (19.67%) followed by ethyl oleate (18.45%), linolenic acid methyl ester (11.67%), and palmitic acid ethyl ester (11.01%). Tetrazolium 96-well plate MTT assay and agar-well diffusion methods were used to evaluate the isolated oil for its minimum inhibitory concentrations (MIC), minimum bactericidal concentration (MBC), half-maximal inhibitory concentrations (IC50), and zone of inhibitions that could determine the potential antimicrobial efficacy's. Substantial antibacterial activities were observed against the clinical isolates comprising of three Gram-negative bacteria, viz., Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa, and one Gram-positive bacterial strain, Enterococcus faecalis. The oils were also effective against Candida albicans and Fusarium oxysporum when evaluated for their antifungal potential. Moreover, significant antioxidant potential with IC50 values of 136.4 and 161.5 µg/mL for extracted oil was evaluated through DPPH (1,1-Diphenyl-2-picryl-hydrazyl) and ABTS assays compared with standard ascorbic acid where the IC50 values were 44.49 and 67.78 µg/mL, respectively, against the tested free radicals. The oils was also potent, inhibiting the α-glucosidase (IC50 5.45 ± 0.42 µg/mL) enzyme compared to the standard. Anti-glucosidase potential was visualized through molecular docking simulations where ten compounds of the oil were found to be the leading inhibitors of the selected enzyme based on interactions, binding energy, and binding affinity. The oil was found to be an effective anti-inflammatory (61%) agent compared with diclofenac sodium (70.92%) via the carrageenan-induced assay. An appreciable (48.28%) analgesic activity in correlation with the standard aspirin was observed through the acetic acid-induced writhing bioassay. The oil from the n-hexane fraction of S. edelbergii contained valuable bioactive constituents that can act as in vitro biological and in vivo pharmacological agents. However, further studies are needed to uncover individual responsible compounds of the observed biological potentials which would be helpful in devising novel drugs.

Demethyleneberberine: A possible treatment for Huntington's disease.

Huntington disease (HD) is a type of neurodegenerative disease that is characterized by presence of multiple repeats (more than 36) of cytosine-adenine-guanine (CAG) trinucleotides and mutated huntingtin (mHtt). This can further lead to oxidative stress, enhancement in level of ROS/RNS, mitochondrial dysfunction and neuroinflammations. Many clinical and preclinical trials have been conducted so far for the effective treatment of HD however, none of the drugs has shown complete relief. The regeneration of neurons is a very complicated process and associated with multiple pathological pathways. Hence, finding a unique solution using single drug that could act on multiple pathological pathways is really cumbersome. In the proposed hypothesis the use of demethyleneberberine (DMB) as a potential anti-HD agent has been explained. It is a metabolite of berberine and reported to act on multiple mechanistic pathways that are responsible for HD. Present article highlights new mechanistic insights through which DMB inhibits ROS/RNS, oxidative stress, mitochondrial dysfunctions and neuroinflammation such as NFκB, TNF-α, IL-6 and IL-8, cytokinin. Further its action on cellular apoptosis and neuronal cell death are also reported.

Effects of Green cardamom (Elettaria cardamomum Maton) and its combination with cyclophosphamide on Ehrlich solid tumors.

BACKGROUND: Cardamom (Elettaria cardamomum) is a spice and exhibits potent antioxidant and biological activities through distinct molecular mechanisms. However, the anticancer effect of cardamom was not explored yet in Ehrlich solid tumor (EST)-bearing mice. OBJECTIVES: This investigation was aimed to evaluate the anti-cancer effects of green cardamom (GCar) alone or combined with the anti-cancer drug cyclophosphamide in an in vivo model to explore its mechanistic role in tumor cell death in EST-bearing mice. METHODS: Ehrlich ascites tumor cells were injected in the mice and 5 days later the animals treated with GCar and/or cyclophosphamide for 10 days. Twenty-four hours from the last treatment, animals were sacrificed for the different measurements. RESULTS: Data recorded for tumor size, percentage of tumor growth inhibition, tumor growth delay and mean survival time of EST-bearing mice demonstrated the effective role of GCar alone or combined with CPO as a promising anti-cancer agent because it reduced tumor size. GCar elevated the mean survival time of EST-bearing mice compared to that of untreated EST and EST + CPO groups. Analysis of qPCR mRNA gene and protein expression revealed that GCar alone or combined with CPO were promising anticancer agents. After the treatment of EST with GCar, the apoptotic-related genes and proteins were significantly modulated. GCar induced markedly significant decreases in oxidative stress biomarkers and a significant increment in glutathione levels and that of antioxidant enzymes. With a marked diminish in liver and kidney function biomarkers. CONCLUSION: The results revealed that GCar could serve as an apoptotic stimulator agent, presenting a novel and potentially curative approach for cancer treatment, inducing fewer side effects than those of the commercially used anti-cancer drugs, such as CPO.

Fucoidan supplementation modulates hepato-renal oxidative stress and DNA damage induced by aflatoxin B1 intoxication in rats.

Aflatoxins are a common food contaminant of global concern. Aflatoxin B1 (AFB1) intoxication is associated with serious health hazards. Recently, fucoidan (FUC) has gained much attention from pharmaceutical industry due to its promising therapeutic effects. The impacts of FUC on AFB1-induced liver and kidney injures have not been sufficiently addressed. This research was conducted to evaluate the ameliorative effect of FUC in AFB1-induced hepatorenal toxicity model in rats over 14 days. Five groups were assigned; control, FUC (200 mg/kg/day, orally), AFB1 (50 µg/kg, i.p.), and AFB1 plus a low or high dose of FUC. AFB1 induced marked hepatorenal injury elucidated by substantial alterations in biochemical tests and histological pictures. The oxidative distress instigated by AFB1 enhanced production of malondialdehyde (MDA) and nitric oxide (NO) along with reduction in the reduced-glutathione (GSH), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities. DNA damage in the liver and kidney tissues has been demonstrated by overexpression of proliferating cell nuclear antigen (PCNA). Unambiguously, FUC consumption alleviates the AFB1-induced mitochondrial dysfunction, oxidative harm, and apoptosis. These ameliorated effects are proposed to be attributed to fucoidan's antioxidant and anti-apoptotic activities. Our results recommend FUC supplementation to food because it exerts both preventive and therapeutic effects against AFB1-induced toxicity.

Ziziphus spina-christi leaf extract attenuates mercuric chloride-induced liver injury in male rats via inhibition of oxidative damage.

Heavy metal contamination including mercury (Hg) has become one of the most serious environmental problems facing humans and other living organisms. Here, the hepatoprotective effects of Z. spina-christi leaf extract (ZCE) against inorganic mercury salt (mercuric chloride; HgCl2)-induced hepatotoxicity model was investigated in rats. Mercury concentration, liver function markers, oxidative stress markers, inflammation, cell death indicators, and histopathology were assessed. ZCE protected against HgCl2-induced hepatotoxicity, decreased Hg concentration, lipid peroxidation, and nitric oxide, increased glutathione, superoxide dismutase, catalase, and glutathione recycling enzymes (peroxidase and reductase), and upregulated nuclear factor-erythroid 2-related factor 2 (Nrf2) gene expression in HgCl2-intoxicated rat hepatic tissue. Nrf2 downstream gene and heme oxygenase-1 were also upregulated, confirming that hepatoprotection by ZCE against HgCl2-induced liver damage involved activation of the Nrf2/antioxidant response element pathway. ZCE also decreased the expression and production of pro-inflammatory cytokines and pro-apoptotic proteins and increased anti-apoptotic protein Bcl-2. Immunohistochemical analysis of liver tissues of HgCl2-treated rats confirmed the alternations of apoptotic-related protein expression. Our data demonstrated that post-administration of ZCE attenuated HgCl2-induced liver damage by activating the Nrf2/HO-1 signaling pathway. Therefore, administering this extract may be a novel therapeutic strategy for inorganic mercury intoxication.

Moringa oleifera Leaf Extract Attenuates Pb Acetate-induced Testicular Damage in Rats.

BACKGROUND: Lead (Pb) remains a common contaminant in the environment in many parts of the world. Pb exposure adversely affects many human organs, including the gonads, via oxidant and inflammatory marker propagation in affected tissues. Moringa oleifera leaf extract (MOE) is a rich source of antioxidants, reported to have robust anti-inflammatory properties. AIMS: This investigation assessed whether MOE could mitigate testicular damage caused by Pb acetate treatment in rats. METHODS: Four experimental groups were used: control animals (saline only), MOE (MOE only), PbAc (Pb acetate injection only), and MOE+PbAc. All treatments were administered for two weeks, after which animals were sacrificed, and tissues and serum were examined. To confirm the potential antioxidant effect of MOE, the total polyphenolic (TP) and flavonoid (TF) concentrations were determined. RESULTS: The obtained results revealed that the TP concentration was 17.4 mg gallic acid equivalents per gram MOE dried weight and the TF concentration was 5.6 mg of quercetin equivalents per gram MOE dried weight. Moreover, MOE partially restored levels of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) and testosterone and significantly attenuated oxidative stress biomarkers, malondialdehyde (MDA) and nitric oxide (NO), compared to levels observed in the PbAc-only group. MOE significantly increased the enzymatic and non-enzymatic antioxidant molecules superoxide dismutase (SOD) and catalase (CAT), glutathione peroxidase (GPx) and glutathione reductase (GR), and glutathione (GSH). Testicular levels of inflammatory cytokines tumor necrosis factor-alpha (TNFα) and interleukin-1beta (IL-1ß) were significantly decreased in MOE+PbAc compared to PbAc. MOE also significantly decreased pro-apoptotic Bax and caspase- 3 mRNA and protein levels and increased anti-apoptotic Bcl-2 mRNA and protein levels. CONCLUSION: MOE extract was associated with significant antioxidant, anti-inflammatory, and anti- apoptotic activity that ameliorated testicular damage induced by Pb acetate. MOE is proposed as a favorable adjuvant to existing treatments for Pb-induced toxicity.

Moringa oleifera ethanolic extract attenuates tilmicosin-induced renal damage in male rats via suppression of oxidative stress, inflammatory injury, and intermediate filament proteins mRNA expression.

Tilmicosin (Til) is a popular macrolide antibiotic, widely used in veterinary practice. The present study was designed to address the efficacy of Moringa oleifera ethanolic extract (MOE) in protecting against Tilmicosin (Til) - induced nephrotoxicity in Sprague Dawley rats. Animals were treated once with Til (75 mg/kg bw, subcutaneously), and/or MOE for 7 days (400 or 800 mg/kg bw, by oral gavage). Til-treatment was associated with significantly increased serum levels of creatinine, urea, sodium, potassium and GGT activity, as well as decreased total protein and albumin concentrations. Renal tissue hydrogen peroxide (H2O2) and malondialdehyde (MDA) levels were elevated, while the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) enzymes were diminished. The levels of renal tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß) and the mRNA expression of intermediate filament protein encoding genes (desmin, nestin and vimentin) in the kidney were up- regulated with histopathological alterations in renal glomeruli, tubules and interstitial tissue. These toxic effects were markedly ameliorated by co-treatment of MOE with Til, in a dose dependent manner. Taken together, these results indicate that MO at 800 mg/kg protects against Til-induced renal injury, likely by its potent antioxidant and anti-inflammatory properties, which make it suitable to be used as a protective supplement with Til therapy.

Protective effects of Artemisia judaica extract compared to metformin against hepatorenal injury in high-fat diet/streptozotocine-induced diabetic rats.

Diabetes mellitus (DM) is one of the most dangerous incurable diseases that affects a large number of people worldwide. Artemisia species have various protective activities and are widely used for the control of diabetes in folkloric medicine. Therefore, the current study was designed to illustrate the protective effect of oral administration of Artemisia judaica extract (AjE) against hepatorenal damage in a high-fat diet/streptozotocin (HFD/STZ) rat model of hyperlipidemia and hyperglycemia. Animals were divided into five groups-control, AjE, HFD/STZ, HFD/STZ-AjE (300 mg/kg), and HFD/STZ-MET (100 mg/kg)-and treated daily for 28 days. The results revealed that STZ-injected rats showed marked hyperglycemia and hypoinsulinemia in addition to high levels of cholesterol, triglycerides, and low- and high-density lipoproteins compared to control rats. Significant elevations in hepatic (AST and ALT) and renal (urea, uric acid, and creatinine) function markers were observed in the serum of diabetic rats. Additionally, STZ injection caused remarkable elevations in lipid peroxidation and nitric oxide levels as well as suppression of antioxidant markers (superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, and glutathione). Marked elevations in TNF-α and Bax levels with a decline in Bcl-2 levels were detected after STZ injection. Furthermore, TGF-ß1 expression levels were significantly upregulated in the liver and kidney tissues. Rats that received AjE or MET showed significant improvement in most of the aforementioned parameters, and the protective efficacy was higher for AjE than for MET. Histopathological screening confirmed the biochemical findings. Conclusively, our results illustrated the antihyperglycemic, antihyperlipidemic, antioxidant, anti-inflammatory, and antiapoptotic activities of AjE against hepatorenal injury in HFD/STZ-induced diabetes.

Alleviation of lead acetate-induced nephrotoxicity by Moringa oleifera extract in rats: highlighting the antioxidant, anti-inflammatory, and anti-apoptotic activities.

Lead (Pb) is an environmental toxicant; its consumption can induce renal deficits. In this study, we explored the possible protective efficiency of Moringa oleifera extract (MOE) against lead acetate (PbAc)-mediated reprotoxicity. Four experimental groups of seven rats each were used: control, PbAc, MOE, and MOE+PbAc groups. All groups were given their respective treatment for 4 weeks. PbAc impaired the oxidative/antioxidative balance in the renal tissue, as shown by the decreased antioxidant proteins (glutathione, glutathione reductase, glutathione peroxidase, catalase, and superoxide dismutase) and increased oxidants (lipid peroxidation and nitric oxide). Additionally, PbAc enhanced the progression of kidney inflammation by increasing tumor necrosis factor-alpha, interleukin-1 beta, and nuclear factor kappa B associated with upregulation of inducible nitric oxide synthase. Moreover, a dysregulation in the apoptotic-regulating proteins (Bax, caspase-3, and Bcl2) were recorded upon PbAc exposure. Remarkably, MOE oral administration restored redox homeostasis, suppressed the inflammatory and apoptotic responses in the kidney tissue. Our findings point out that MOE could be used as an alternative remedy to overcome the adverse effects of Pb exposure, which may be due to its potent antioxidant, anti-inflammatory, and anti-apoptotic effects.

Effect of Moringa oleifera Lam. methanolic extract on lead-induced oxidative stress-mediated hepatic damage and inflammation in rats.

This experiment explored the potential hepatic protective effect of Moringa oleifera Lam. methanolic extract (MOE) against lead-induced hepatotoxicity. Thirty-two adult Wistar albino rats were allocated randomly equally into four groups, seven rats each. The control group received intraperitoneal (i.p.) injections of physiological saline (0.9% NaCl); the lead acetate (Pb) group was i.p. injected with 20 mg/kg of Pb; the MOE group was orally administered with 250 mg/kg of MOE; and the MOE+ Pb group was orally treated with 250 mg/kg of MOE 3 h before receiving i.p. injections of 20 mg/kg Pb. All rats received their treatment for 14 days. Results revealed that Pb(II) intoxication induced liver injury accompanied by elevated levels of liver function markers (ALT and AST), oxidative stress markers (MDA and NO), and proinflammatory cytokines (NF-κB p65, TNFα, and IL-1ß as well iNOS expression) in addition to the pro-apoptotic-related proteins such as Bax and caspase-3. Meanwhile, significantly depleted GSH content, suppressed activity of antioxidant enzyme activity, and anti-apoptotic protein Bcl-2 were also manifested in the liver tissue. Interestingly, concurrent treatment of rats with MOE ameliorated liver markers, prevented tissue injury, and inhibited oxidative stress, apoptosis, and NF-κB. In addition, MOE activated the detoxifying enzyme system in Pb(II)-intoxicated rats. Therefore, the obtained results in the present experiment provide evidence that MOE concurrent administration has the potential to protect the liver tissues in Pb(II)-intoxicated rats by preventing oxidative stress, inflammation, and apoptosis, via attenuation of NF-κB signaling pathway.

The Potential Protective Effect of Orange Peel and Selenium against 17ß-Estradiol- Induced Chronic Non-Bacterial Prostatitis in Rats.

BACKGROUND: Prostate Cancer (PCa) is defined as a major health problem faced by the male population. AIM: We aimed to investigate the protective effects of Orange Peel Extract (OPE) and/or Selenium (Se) on chronic non-bacterial prostatitis in a rat model. METHODS: Fifty-six adult male Wistar albino rats were castrated; after 5 days, they were divided randomly into eight groups (n= 7). The control group received saline treatment; while 17ß-estradiol (E2) (0.25mg/kg) was injected subcutaneously in rats from Groups V, VI, VII, and VIII to induce chronic non-bacterial prostatitis. They were then treated with OPE (400mg/kg body weight; Groups II, IV, VI, and VIII) and/or sodium selenite (0.5mg/kg body weight; Groups III, IV, VII, and VIII) for 30 days. Interleukin-2 (IL2) and Prostate Cancer Antigen 3 (PCA3) mRNA expressions were determined using qPCR; Prostate-Specific Antigen (PSA) protein expression was determined immunohistochemically. Prostate tissue histology was examined by hematoxylin and eosin staining, and the levels of oxidative stress markers and antioxidant enzymes were measured. RESULTS: E2 administration significantly increased IL2 and PCA3 mRNA expressions, and PSA protein expression. It also increased the prostate wet weight and body weight, and lipid peroxidation, nitric oxide, TNF-α, and IL-1ß levels, decreased the glutathione and antioxidant enzyme levels and caused distinct histological alterations in the prostate gland. OPE and/or Se markedly improved all the studied parameters due to their antioxidant properties and anti-inflammatory effects. CONCLUSION: OPE and Se showed protective effects against 17ß-estradiol-induced chronic non-bacterial prostatitis. These results suggest that protection of chronic non-bacterial prostatitis by OPE+Se combination involves anti-oxidation and anti-inflammation. Moreover, their synergistic mechanism was mostly achieved via the regulation of oxidative stress and inflammation processes.

Red Beetroot Extract Abrogates Chlorpyrifos-Induced Cortical Damage in Rats.

Organophosphorus insecticides including chlorpyrifos (CPF) are mainly used for agriculture, household, and military purposes; their application is associated with various adverse reactions in animals and humans. This study was conducted to evaluate the potential neuroprotective effect of red beetroot methanolic extract (RBR) against CPF-induced cortical damage. Twenty-eight adult male Wistar albino rats were divided into 4 groups (n = 7 in each group): the control group was administered physiological saline (0.9% NaCl), the CPF group was administered CPF (10 mg/kg), the RBR group was administered RBR (300 mg/kg), and the RBR+CPF group was treated with RBR (300 mg/kg) 1 hr before CPF (10 mg/kg) supplementation. All groups were treated for 28 days. Rats exposed to CPF exhibited a significant decrease in cortical acetylcholinesterase activity and brain-derived neurotrophic factor and a decrease in glial fibrillary acidic protein. CPF intoxication increased lipid peroxidation, inducible nitric oxide synthase expression, and nitric oxide production. This was accompanied by a decrease in glutathione content and in the activities of glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase in the cortical tissue. Additionally, CPF enhanced inflammatory response, indicated by increased levels and expression of interleukin-1ß and tumor necrosis factor-α. CPF triggered neuronal apoptosis by upregulating Bax and caspase-3 and downregulating Bcl-2. However, RBR reversed the induced neuronal alterations following CPF intoxication. Our findings suggest that RBR can minimize and prevent CPF neurotoxicity through its antioxidant, anti-inflammatory, and antiapoptotic activities.

Ziziphus spina-christi leaf extract attenuates mercury chloride-induced testicular dysfunction in rats.

Mercury (Hg) is a heavy metal toxicant, causing several adverse reactions to animals and humans including reproductive dysfunction. The potential protective role of Ziziphus spina-christi leaf extract (ZSCLE) against testicular impairments associated with mercury chloride (HgCl2) exposure in rats was investigated in the current study. Four experimental groups were employed as follows (n = 7): group I served as control, group II was gavaged with ZSCLE (300 mg/kg), group III was administered with HgCl2 (0.4 mg/kg), and group IV was preadministered with ZSCLE 1 h before HgCl2. All groups were treated daily for 28 days. The exposure to HgCl2 caused a marked increase in Hg concentration in the testicular tissue, which was accompanied with a decrease in testis index. A reproductive impairment was recorded following HgCl2 exposure as verified through the decrease in levels of testosterone, luteinizing, and follicle-stimulating hormones. HgCl2 was found to enhance the development of oxidative damage in the testicular tissue as presented by the imbalance between pro-oxidants and antioxidant molecules. In addition, excessive release of tumor necrosis factor-α and interleukin-1ß was recorded in response to HgCl2 intoxication. Furthermore, a disturbance in the apoptotic proteins in favor of the pro-apoptotic proteins was also observed following HgCl2 intoxication. However, ZSCLE administration along with HgCl2 abolished significantly the molecular, biochemical, and histopathological alterations induced by HgCl2 intoxication. Our findings suggest that ZSCLE could be used to mitigate reproductive dysfunction associated with HgCl2 exposure.

Nephroprotective Role of Selenium Nanoparticles Against Glycerol-Induced Acute Kidney Injury in Rats.

Acute kidney injury (AKI) is a clinical syndrome associated with the incidence of rhabdomyolysis (RM). The current study was carried out to evaluate whether selenium nanoparticles (SeNPs) can protect against the glycerol-induced AKI model. Rats were distributed into four equal groups (n = 7): the control group (G1), SeNPs group (G2), AKI group (G3), and SeNPs+AKI group (G4). Rats in G1 were intramuscularly injected with physiological saline (0.9% NaCl). Rats in G2 were gavaged with SeNPs (0.1 mg/kg) for 14 days. Rats in G3 were intramuscularly injected with 50% glycerol (10 ml/kg). Rats in G4 were administered with SeNPs for 14 days and then injected with glycerol, as in G3. Glycerol-injected rats showed a significant increase in the kidney relative weight, as well as in the serum urea, creatinine, Kim-1, and renal malondialdehyde, nitric oxide, TNF-α, IL-1ß, cytochrome c, Bax, and caspase-3 levels. In addition, a significant decrease in glutathione, glutathione peroxidase, glutathione reductase, superoxide dismutase, and catalase was recorded in the renal tissue. Selenium nanoparticles reduced the biochemical, molecular, and histological changes produced by glycerol. Overall, our results suggest that selenium nanoparticles could be used to protect against AKI development via antioxidant, anti-inflammatory, and anti-apoptotic activities.