Alleviation of microcystin-leucine arginine -induced hepatotoxicity: An updated overview.

OBJECTIVES: Contamination of surface waters is a major health threat for all living creatures. Some types of blue-green algae that naturally occur in fresh water, are able to produce various toxins, like Microcystins (MCs). Microcystin-leucine arginine (MC-LR) produced by Microcystis aeruginosa is the most toxic and abundant isoforms of MCs, and it causes hepatotoxicity. The present article reviews preclinical experiments examined different treatments, including herbal derivatives, dietary supplements and drugs against MC-LR hepatotoxicity. METHODS: We searched scientific databases Web of Science, Embase, Medline (PubMed), Scopus, and Google Scholar using relevant keywords to find suitable studies until November 2023. RESULTS: MC-LR through Organic anion transporting polypeptide superfamily transporters (OATPs) penetrates and accumulates in hepatocytes, and it inhibits protein phosphatases (PP1 and PP2A). Consequently, MC-LR disturbs many signaling pathways and induces oxidative stress thus damages cellular macromolecules. Some protective agents, especially plants rich in flavonoids, and natural supplements, as well as chemoprotectants were shown to diminish MC-LR hepatotoxicity. CONCLUSION: The reviewed agents through blocking the OATP transporters (nontoxic nostocyclopeptide-M1, captopril, and naringin), then inhibition of MC-LR uptake (naringin, rifampin, cyclosporin-A, silymarin and captopril), and finally at restoration of PPAse activity (silybin, quercetin, morin, naringin, rifampin, captopril, azo dyes) exert hepatoprotective effect against MC-LR.

Occupational respiratory disorders in Iran: a review of prevalence and inducers.

The link between occupational respiratory diseases (ORD) and exposure to harmful factors that are present in the workplace has been well shown. Factors such as physical activity, age and duration of occupational exposure playing important roles in ORD severity, should be identified in the workplace, their effects on workers health should be studied, and ultimately, exposure to them must be minimized. We carried out a literature review by searching PubMed, Scopus, and Web of Science databases to retrieve studies published from 1999 until the end of April 2023 reporting the prevalence and inducers of ORD in Iran. In Iranian workers, several ORD such as interstitial lung disease, silicosis, occupational asthma, pulmonary inflammatory diseases, chronic obstructive pulmonary diseases, and lung cancers have been reported. It was indicated that ORD mainly occur due to repeated and prolonged exposure to noxious agents in the workplace. We also extracted the prevalence of ORD in different regions of Iran from the retrieved reports. Based on our literature review, the prevalence of ORD among Iranian workers highlights the importance of regular assessment of the risk of exposure to noxious agents in the workplace to develop measures for preventing potential adverse effects.

Hormetic effects of curcumin on oxidative stress injury induced by trivalent arsenic in isolated rat hepatocytes.

Objective: Arsenic (As) poisoning is a worldwide public health problem. Arsenic can cause cancer, diabetes, hepatic problems, etc. Hence, we investigated possible hepatoprotective properties of curcumin against As3+-induced liver damages in freshly isolated rat hepatocytes. Materials and Methods: Isolation of hepatocytes was done by the two-step liver perfusion method using collagenase. The EC50 concentration of As3+ was used in toxicity assessments and curcumin (2, 5, and 10 µM) was added 15 min before As3+ addition to isolated hepatocytes. Curcumin impact was assessed in terms of cytotoxicity, lipid peroxidation induction, reactive oxygen species (ROS) levels, and mitochondrial membrane potential. Results: As3+ significantly increased cytotoxicity, malondialdehyde and ROS levels and induced mitochondrial membrane damage and hepatocyte membrane lysis after 3 hr incubation. Curcumin 2 µM significantly prevented lipid peroxidation induction, ROS formation, and mitochondrial membrane damage; while curcumin 5 µM had no apparent effect on these parameters, curcumin 10 µM potentiated them. Conclusion: Curcumin only at low doses could ameliorate oxidative stress injury induced by As3+ in isolated rat hepatocytes.

Pharmacological effects of Safranal: An updated review.

Safranal (a monoterpene aldehyde) is the major volatile component of saffron which is responsible for the saffron unique odor. Several studies have shown the pharmacological activities of safranal including anti-oxidant, anti-inflammatory, cardioprotective, neuroprotective, nephroprotective, gastrointestinal protective, etc. This study was designed to review the pharmacological and medical effects of safranal and up-to-date previous knowledge. Moreover, some patents related to the pharmacological effects of safranal were gathered. Therefore, electronic databases including Web of Sciences, Scopus, and Pubmed for pharmacological effects and US patent, Patentscope, and Google Patent for patents were comprehensively searched by related English keywords from 2010 to June 2022. According to our review, most of the studies are related to the safranal effects on CNS such as antianxiety, analgesic, anticonvulsant, antiischemic, anti-tremor, memory enhancement and its protective effects on neurodegenerative disorders such as Alzheimer's, Parkinson and Huntington diseases. Other effects of safranal are antiasthmatic, antihypertensive, antiaging, anticataract, etc. Moreover, the protective effects of this agent on metabolic syndrome and diabetic nephropathy have been shown. Different mechanisms including anti-oxidant, anti-inflammatory, muscle relaxation, antiapoptotic, and regulatory effects on the genes and proteins expression related to signaling pathways of oxidative stress, inflammation, apoptosis, proliferation, etc. are involved in safranal pharmacological effects. Some patents for the prevention and/or treatment of different diseases such as liver cancer, sleep disorder, depression, cognitive disorder, obesity and PMS were also included. Based on the documents, safranal is considered a promising therapeutic agent although more clinical studies are needed to verify the beneficial effects of safranal in humans.

Probabilistic risk assessment of exposure to multiple mycotoxins in consumers of packaged and unpackaged spices in Iran.

The current study assessed the risk posed to Iranian consumers by oral exposure to a mixture of ten mycotoxins in 138 packaged and unpackaged spices collected from the Iran market. Concentrations of mycotoxins in samples were quantified by liquid chromatography, tandem mass spectrometry with triple quadrupole, and ion trap. Probabilistic health risks of oral exposure to these mycotoxins for Iranians were assessed under percent tolerable daily intake (TDI) and cancer risk scenarios. Mean concentrations of mycotoxins in both packaged and unpackaged spice samples showed statistically significant variation among different spice samples. Based on a Monte Carlo simulation model, at the 50th, 80th, and 95th centiles, oral consumption of the analyzed samples poses no carcinogenic risk for exposure to aflatoxin. Moreover, in both packaged and unpackaged samples, while the percent TDIs for ochratoxin A, deoxynivalenol, zearalenone, patulin, fumonisin B1, and fumonisin B2 were below 1.0 at the 50th, 80th, and 95th centiles, the value was above 1.0 for aflatoxin B1, aflatoxin B2, aflatoxin G1, and aflatoxin G2 at each of these centiles.

Exposure to anesthetic gases in the operating rooms and assessment of non-carcinogenic risk among health care workers.

Health care workers employed operating room in hospital and health centers are unavoidably exposed to inhaling toxic gases, including isoflurane and sevoflurane. Chronic contact with these gases increases the risk of spontaneous abortion, congenital anomalies and cancers. Risk assessment is an important tool in predicting the possible risk to personnel's health. Therefore, this study was conducted with the aim of determining the concentration of isoflurane and sevoflurane gas in the air of the operating room and estimating the non-carcinogenic risk caused by them. In this descriptive-cross-sectional study, according to the occupational method (OSHA 103), 23 samples (isoflurane and sevoflurane) were collected in the air of operating rooms of four selected hospitals in Ahvaz city by using SKC sampling pumps and sorbent tube (Anasorb 747). The samples were determined by used to gas chromatography with a flame ionization detector (GC/FID). Statistical analysis, including the Kruskal-Wallis test, was used to compare the average concentration of anesthetic gases, and the one-sample t-test was used to compare the average with the standard level. In all analyses, the significance level was 0.05, which was performed by SPSS version 22 software. Result of this study showed that the average concentration of isoflurane in private and general hospitals were 23.636 and 17.575 ppm, respectively. Also, the average level of sevoflurane were 1.58 and 7.804 ppm. According to the results the mean amount of anesthetic gases was within the range recommended by Iran's Occupational and Environmental Health Center and the permissible threshold limit provided by ACGIH. In addition, non-cancer risks from occupational exposure to isoflurane and sevoflurane in selected private and general hospitals were acceptable (HQ < 1). Although the results show that overall occupational exposure to anesthetic gases is less than acceptable but long-term exposure to anesthetic gases may endanger the health of operating room staffs. Therefore, it is recommended to implement some technical controls, including regular inspection of ventilation systems, the use of advanced ventilation systems with high cleaning power, continuous control of anesthesia devices in terms of leakage, and periodic training of related staff.

Oral Nicorandil effectively attenuates the incidence of contrast-induced nephropathy in patients undergoing cardiac catheterization: a randomized, controlled, open-label clinical trial.

PURPOSE: The contrast-induced nephropathy (CIN) rate is increasing globally and can increase the rate of mortality and long-term problems. This study aims to determine the effect of Nicorandil on preventing CIN among patients undergoing cardiac catheterization. METHODS: In a controlled randomized open-labeled clinical trial, all included patients undergoing cardiac catheterization due to coronary problems and possessing at least two risk factors of contrast nephropathy were divided into two groups of intervention and control. The intervention group received oral Nicorandil and normal saline, while the control group was treated with intravenous normal saline. Serum creatinine was measured before and 48 h after the procedure, and patients were assessed regarding CIN. RESULTS: In this study, 172 patients entered each group; 41.86% and 45.34% were male in the control and Nicorandil groups. We showed that the incidence of CIN was meaningfully lower in the Nicorandil group (12, 7%) than in the control group (34, 19.8%, P = 0.001). Additionally, the incidence of CIN was notably lower in the female patients in the Nicorandil (85.7%) than in the control group (14.3%, P = 0.001); however, these numbers were not significantly different among men (64.0% and 36.0%, respectively, P = 0.850). After the injection of the contrast agent, the serum levels of blood urea nitrogen (P = 0.248), creatinine (P = 0.081), and glomerular filtration rate (P = 0.386) showed no significant differences between the control and Nicorandil groups. Multivariate regression analysis showed that Nicorandil significantly lowered the odds of CIN [odds ratio (OR) = 0.299, 95% confidence interval (CI) 0.149-0.602; P = 0.001] after adjustment for baseline creatinine (OR = 1.404, 95% CI 0.431-4.572; P = 0.574). CONCLUSION: Our results indicate that pre-procedural treatment with Nicorandil may be effective against CIN in contrast to agent-exposed patients.

Natural compounds regulate the PI3K/Akt/GSK3ß pathway in myocardial ischemia-reperfusion injury.

The PI3K/Akt/GSK3ß pathway is crucial in regulating cardiomyocyte growth and survival. It has been shown that activation of this pathway alleviates the negative impact of ischemia-reperfusion. Glycogen synthase kinase-3 (GSK3ß) induces apoptosis through stimulation of transcription factors, and its phosphorylation has been suggested as a new therapeutic target for myocardial ischemia-reperfusion injury (MIRI). GSK3ß regulatory role is mediated by the reperfusion injury salvage kinase (RISK) pathway, and its inhibition by Akt activation blocks mitochondrial permeability transition pore (mPTP) opening and enhances myocardial survival. The present article discusses the involvement of the PI3K/Akt/GSK3ß pathway in cardioprotective effects of natural products against MIRI.Abbreviations: Akt: protein kinase B; AMPK: AMP-activated protein kinase; ATP: adenosine triphosphate; Bad: bcl2-associated agonist of cell death; Bax: bcl2-associated x protein; Bcl-2: B-cell lymphoma 2; CK-MB: Creatine kinase-MB; CRP: C-reactive-protein; cTnI: cardiac troponin I; EGCG: Epigallocatechin-3-gallate; Enos: endothelial nitric oxide synthase; ER: endoplasmic reticulum; ERK ½: extracellular signal­regulated protein kinase ½; GSK3ß: glycogen synthase kinase-3; GSRd: Ginsenoside Rd; GSH: glutathione; GSSG: glutathione disulfide; HO-1: heme oxygenase-1; HR: hypoxia/reoxygenation; HSYA: Hydroxysafflor Yellow A; ICAM-1: Intercellular Adhesion Molecule 1; IKK-b: IκB kinase; IL: interleukin; IPoC: Ischemic postconditioning; IRI: ischemia-reperfusion injury; JNK: c-Jun N-terminal kinase; Keap1: kelch-like ECH-associated protein- 1; LDH: lactate dehydrogenase; LVEDP: left ventricular end diastolic pressure; LVP: left ventricle pressure; LVSP: left ventricular systolic pressure; MAPK: mitogen-activated protein kinase; MDA: malondialdehyde; MIRI: myocardial ischemia-reperfusion injury; MnSOD: manganese superoxide dismutase; mPTP: mitochondrial permeability transition pore; mtHKII: mitochondria-bound hexokinase II; Nrf-1: nuclear respiratory factor 1; Nrf2: nuclear factor erythroid 2-related factor; NO: nitric oxide; PGC-1α: peroxisome proliferator­activated receptor γ coactivator­1α; PI3K: phosphoinositide 3-kinases; RISK: reperfusion injury salvage kinase; ROS: reactive oxygen species; RSV: Resveratrol; SOD: superoxide dismutase; TFAM: transcription factor A mitochondrial; TNF-α: tumor necrosis factor-alpha; VEGF-B: vascular endothelial growth factor B.

Assessment of Carcinogenic and Non-carcinogenic Risk of Exposure to Metals via Consumption of Coffee, Tea, and Herbal Tea in Iranians.

In the current study, we assessed health risk posed to Iranian consumers through exposure to metals via oral consumption of coffee, tea, and herbal tea of various trademarks collected from Iran market. Level of As, Cd, Cr, Cu, Fe, Hg, Ni, and Pb in 243 samples was quantified by inductively coupled plasma-optical emission spectrometry (ICP-OES). The metal levels in coffee samples from different trademarks of a specific country had statistically similar levels of metals; however, metal levels differed significantly among brand names form different countries. Metal levels in tea samples differed significantly between domestic and imported products, while different trademarks of similar countries did not show significant variations in this respect. Metal level in herbal tea samples did not show significant variations among different trademarks. Nevertheless, it should be highlighted that mean concentrations of metals statistically differed among different herbal tea samples. Deterministic hazard quotients (HQs) were <1.0 for all non-carcinogenic metals and total hazard index (HI) values indicated no risk; however, probabilistic assessment calculated HI values >1. In both deterministic and probabilistic scenarios, carcinogenic metals As and Ni had an estimated incremental lifetime cancer risk (ILCR) of medium level while that of Pb indicated no cancer risk. Sensitivity analysis showed that the concentration of metals had the most significant effect on non-carcinogenic and carcinogenic risks.

Probabilistic risk assessment of exposure to multiple metals and pesticides through consumption of fruit juice samples collected from Iranian market.

The current study assessed the risk posed to Iranian consumers by oral exposure to a mixture of 20 pesticides and six metals in 96 fruit juice (FJ) samples (3 batches × 4 brands × 8 types of FJs) collected from Iran market. Concentrations of metals and pesticides in FJs were quantified by inductively coupled plasma-optical emission spectrometry (ICP-OES) and chromatography-mass spectrometry (GC-MS), respectively. The mean concentration of all pesticides was below the maximum residue limits (MRLs) set by the European Union (EU). The calculated target hazard quotients (THQs) and total hazard index (HI) were <1.0 for all pesticides residue, indicating no risk. For the carcinogenic metals (As, Ni, and Pb), estimated incremental lifetime cancer risks (ILCRs) at the 50th and 95th centiles were respectively 4.25 × 10-5 and 5.30 × 10-5 (for As), 2.85 × 10-5 and 3.71 × 10-5 (for Ni), and 2.84 × 10-8, and 3.97 × 10-8 (for Pb), indicating no risk. At the 50th and 95th centiles, HI for non-carcinogenic metals (Cd, Hg, and Cr) was <1.0, indicating no risk. Based on sensitivity analyses of the input variables, the concentration of metals and pesticides, and the FJs ingestion rate had significant influential impacts on the calculated THQ and HI.

Effects of gallic acid on intraperitoneal adhesion bands in rats.

Objective: Gallic acid (GA) is an organic acid that possesses anti-inflammatory effects as it inhibits the production of metalloproteinases, tissue plasminogen activator, growth factors and adhesion molecules. Since formation of abdominal surgery-induced adhesion bands is accompanied by inflammation, angiogenesis and cell proliferation, in the current study, we assessed potential beneficial properties of GA against adhesion bands formation in rats. Materials and Methods: Thirty-six adult male rats were assigned into six groups of six animals. After induction of anesthesia, peritoneal injury was induced using a standard method and animals received either GA (10, 25, 50 and 100 mg/kg), or normal saline, while a group of rats remained intact. Seven days after the surgery, animals were decapitated and samples were collected for pathology evaluations. Also, lipid peroxidation (TBARS) and tumor necrosis factor alpha (TNF-α) levels were determined in serum samples. Results: Our results showed that GA significantly reduced lipid peroxidation in serum samples but had no effect on TNF-α levels. Furthermore, microscopic and macroscopic injuries reduced significantly in GA-treated animals. Conclusion: Since GA reduced adhesion bands formation at microscopic and macroscopic levels, it could be considered a treatment against adhesion bands formation.

A review of the protective effects of chlorogenic acid against different chemicals.

Chlorogenic acid (CGA) is a naturally occurring non-flavonoid polyphenol found in green coffee beans, teas, certain fruits, and vegetables, that exerts antiviral, antitumor, antibacterial, and antioxidant effects. Several in vivo and in vitro studies have demonstrated that CGA can protect against toxicities induced by chemicals of different classes such as fungal/bacterial toxins, pharmaceuticals, metals, pesticides, etc., by preservation of cell survival via reducing overproduction of nitric oxide and reactive oxygen species and suppressed pro-apoptotic signaling. CGA antioxidant effects mediated through the Nrf2-heme oxygenase-1 signaling pathway were shown to enhance the levels of antioxidant enzymes such as superoxide dismutase, catalase, glutathione-S-transferases, glutathione peroxidase, and glutathione reductase as well as glutathione content. Also, CGA could suppress inflammation via inhibition of toll-like receptor 4 and MyD88, and the phosphorylation of inhibitor of kappa B and p65 subunit of NF-κB, resulting in diminished levels of downstream inflammatory factors including interleukin (IL)-1 ß, IL-6, tumor necrosis factor-α, macrophage inflammatory protein 2, cyclooxygenase-2, and prostaglandin E2. Moreover, CGA inhibited apoptosis by reducing Bax, cytochrome C, and caspase 3 and 9 expression while increasing Bcl-2 levels. The present review discusses several mechanisms through which CGA may exert its protective role against such agents. Chemical and natural toxic agents affect human health. Phenolic antioxidant compounds can suppress free radical production and combat these toxins. Chlorogenic acid is a plant polyphenol present in the human diet and exerts strong antioxidant properties that can effectively help in the treatment of various toxicities.

Intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevents the H-89-induced spatial learning deficits in Morris water maze.

OBJECTIVES: H-89 (a protein kinase AII [PKA II] inhibitor) impairs the spatial memory in the Morris water maze task in rats. In the present study, we aimed to study the protective effects of nicotine and O-acetyl-L-carnitine against H-89-induced spatial memory deficits. METHODS: Spatial memory impairment was induced by the bilateral intrahippocampal administration of 10 µM H-89 (dissolved in dimethyl sulfoxide, DMSO) to rats. The rats then received bilateral administrations of either nicotine (1 µg/µL, dissolved in saline) or O-acetyl-L-carnitine (100 µM/side, dissolved in deionized water) alone and in combination. Control groups received either saline, deionized water, or DMSO. RESULTS: The H-89-treated animals showed significant increases in the time and distance travelled to find hidden platforms, and there was also a significant decrease in the time spent in the target quadrant compared to DMSO-treated animals. Nicotine and O-acetyl-L-carnitine had no significant effects on H-89-induced spatial learning impairments alone, but the bilateral intrahippocampal co-administration of nicotine and O-acetyl-L-carnitine prevented H-89-induced spatial learning deficits and increased the time spent in the target quadrant in comparison with H-89-treated animals. CONCLUSIONS: Our results indicated the potential synergistic effects of nicotine and O-acetyl-L-carnitine in preventing protein kinase AII inhibitor (H-89)-induced spatial learning impairments.

A qualitative and quantitative comparison of Crocus sativus and Nigella sativa immunomodulatory effects.

The present article reviews and compares the immunomodulatory activities of Crocus sativus (C. sativus) and Nigella sativa (N. sativa) and their main bioactive compounds. Immunomodulatory effects of these plants, especially with respect to Th1 and Th2 cytokines, are discussed based on relevant articles, books, and conference papers published in English until the end of April 2020, that were retrieved from Web of Science, PubMed, Scopus and Google Scholar databases. C. sativus and its constituents increase immunoglobulin (Ig-)G, interleukin 2 (IL)-2, interferon gamma (IFN-γ), and IFN-γ/IL-4 ratio, but decreased IgM, IL-10 and IL-4 secretion. N. sativa extract and thymoquinone reduce the levels of IL-2, -4, -10, and -12, while enhance IFN-γ and serum IgG1 and 2a. The reviewed articles indicate that C. sativus and N. sativa and their constituents could be potentially considered promising treatments for disorders associated with immune-dysregulation such as asthma and cancer.

A review on the protective effects of naringenin against natural and chemical toxic agents.

Naringenin (NRG), as a flavanone from flavonoids family, is widely found in grapefruit, lemon tomato, and Citrus fruits. NRG has shown strong anti-inflammatory and antioxidant activities in body organs via mechanisms such as enhancement of glutathione S-transferase (GST), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activity, but reduction of serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and malondialdehyde (MDA). Furthermore, NRG anti-apoptotic potential was indicated to be mediated by regulating B-cell lymphoma (Bcl-2), Bcl-2-associated X protein (Bax) and caspase3/9. Overall, these properties make NRG a highly fascinating compound with beneficial pharmacological effects. Based on the literature, NRG-induced protective effects against toxicities produced by natural toxins, pharmaceuticals, heavy metals, and environmental chemicals, were mainly mediated via suppression of lipid peroxidation, oxidative stress (through boosting the antioxidant arsenal), and inflammatory factors (e.g., TNF-α, interleukin [IL]-6, IL-10, and IL-12), and activation of PI3K/Akt and MAPK survival signaling pathways. Despite considerable body of evidence on protective properties of NRG against a variety of toxic compounds, more well-designed experimental studies and particularly, clinical trials are required before reaching a concrete conclusion. The present review discusses how NRG protects against the above-noted toxic compounds.

Polycyclic aromatic hydrocarbons, pesticides, and metals in olive: analysis and probabilistic risk assessment.

In the present study, levels of 22 pesticides, eight metals, and 16 polycyclic aromatic hydrocarbons (PAHs) in 1800 Iranian olive samples (20 cultivars from six different cultivation zones), were determined; then, health risk posed by oral consumption of the olive samples to Iranian consumers was assessed. Quantification of PAHs and pesticides was done by chromatography-mass spectrometry (GC-MS), and metal levels were determined using inductively coupled plasma-optical emission spectrometry (ICP-OES). There were no significant differences among the cultivars and zones in terms of the levels of the tested compounds. Target hazard quotients (THQ) were <1.0 for all pesticides, and total hazard indices (HI) indicated di minimis risk. At the 25th or 95th centiles, Incremental Life Time Cancer Risks (ILCRs) for carcinogenic elements, arsenic, and lead and noncarcinogenic metals did not exhibit a significant hazard (HI <1.0 for both cases). At the 25th or 95th centiles, ILCR and margins of exposure (MoE) for PAHs indicated di minimis risk. Sensitivity analysis showed that concentrations of contaminants had the most significant effect on carcinogenic and noncarcinogenic risks.

Anti-inflammatory, anti-oxidant, and immunomodulatory activities of the genus Ferula and their constituents: A review.

Ferula is a genus of the family Apiaceae and it includes around 170 species of flowering plants mostly native to the Mediterranean region and eastern to central Asia. In Iran, Ferula spp. are widely used in cuisine and traditional medicine. This review discusses the anti-inflammatory, anti-oxidant, and immunomodulatory activities of different species of Ferula. To prepare the present review, Scopus, Google Scholar, PubMed, and Web of Science scientific databases were searched to retrieve relevant articles published from 1985 until December 2020. Based on our literature review, Ferula plants and their derivatives decrease the levels of inflammatory mediators and exert anti-apoptotic effects. Under oxidative stress conditions, these plants and their constituents were shown to decrease oxidative markers such as malondialdehyde, reactive oxygen species, and nitric oxide but increase superoxide dismutase, glutathione peroxidase, catalase activity, and glutathione level. Ferula plants and their constituents also showed immunomodulatory effects by affecting various cytokines. Besides, in vivo and in vitro studies showed hypotensive, neuroprotective, memory-enhancing, anti-oxidant, hepatoprotective, antimicrobial, anticarcinogenic, anticytotoxic, antiobesity, and anthelmintic effects for various species of Ferula and their constituents. These plants also showed a healing effect on gynecological issues such as miscarriage, unusual pain, difficult menstruation, and leukorrhea. All these beneficial effects could have resulted from the anti-inflammatory, anti-oxidant, and immunomodulatory effects of these plants and their constituents. Based on the available literature, members of the genus Ferula can be regarded as potential therapeutics against inflammatory conditions, oxidative stress, and immune dysregulation.

Mangiferin offers protection against deleterious effects of pharmaceuticals, heavy metals, and environmental chemicals.

Mangiferin (MGF) is a polyphenolic C-glucosyl-xanthone extracted from the mango tree (Mangifera indica). MGF has shown diverse effects such as antioxidant, antiapoptotic, radical scavenging, and chelating properties. MGF also has been shown to modulate inflammatory pathways. In this review, we examined and evaluated the literature dealing with the protective effects of MGF against various chemical toxicities. Our literature review indicated that the MGF-induced protective effects against the toxic effects of pharmaceuticals, heavy metals and environmental chemicals were mainly mediated via suppression of lipid peroxidation, oxidative stress (along with enhancement of the antioxidant enzyme), inflammatory factors (TNF-α, IL-6, IL-10, and IL-12), and activation of PI3K/Akt and the MAPK survival signaling pathway.