Attenuation of acrylamide-induced neurotoxicity by supplementation of sitagliptin in Wistar rats.

Objectives: Acrylamide (ACR) induces neurotoxicity in humans and animals through different mechanisms. Sitagliptin is a type-2 diabetes medication with neuroprotective properties. The effects of sitagliptin against neurotoxicity stimulated by ACR were examined. Materials and Methods: Male Wistar rats were classified as follows: 1. Control (normal saline, 11 days, IP), 2. ACR (50 mg/kg, 11 days, IP), 3. ACR (11 days, days 11-20 normal saline), 4-7. ACR+sitagliptin (5, 10, 20, and 40 mg/kg, 11 days, IP), 8. ACR+sitagliptin (10 mg/kg, days 6-11), 9. ACR+sitagliptin (10 mg/kg, days 6-20), 10. Sitagliptin (40 mg/kg, 11 days), 11. ACR+vitamin E (200 mg/kg, IP). Finally, the gait score was evaluated. Reduced glutathione (GSH) and malondialdehyde (MDA) levels were measured in cortex tissue. Also, IL-1ß, TNF-α, and caspase-3 levels were assessed in the cortex by western blotting. Results: ACR caused movement disorders, triggered oxidative stress, and raised TNF-α, IL-1ß, and caspase-3 cleaved levels. Supplementation of sitagliptin (10 mg/kg) along with ACR, in 3 protocols, reduced gait disorders compared to the ACR group. Receiving sitagliptin in all doses plus ACR and injection of sitagliptin (10 mg/kg) from days 6 to11 reduced the MDA level of cortex tissue. Sitagliptin (all doses) plus ACR increased the GSH level of the cortex tissue. Sitagliptin (10 mg/kg) with ACR dropped the amounts of TNF-α and caspase-3 cleaved proteins in cortex tissue but did not affect the IL-1ß level. Conclusion: Sitagliptin disclosed preventive and therapeutic effects on ACR neurotoxicity. Sitagliptin possesses antioxidant, anti-inflammatory, and anti-apoptotic properties and inhibits CR neurotoxicity in rats.

The protective effects of curcumin against cigarette smoke-induced toxicity: A comprehensive review.

Cigarette smoking (CS) is a crucial modifiable risk of developing several human diseases and cancers. It causes lung, bladder, breast, and esophageal cancers, respiratory disorders, as well as cardiovascular and metabolic diseases. Because of these adverse health effects, continual efforts to decrease the prevalence and toxicity of CS are imperative. Until the past decades, the impacts of natural compounds have been under investigation on the harmful effects of CS. Turmeric (Curcuma longa), a rhizomatous herbaceous perennial plant that belongs to the Zingiberaceae family, is the main source of curcumin. This review is an attempt to find out the current knowledge on CS's harmful effects and protective potential of curcumin in the pulmonary, liver, brain, gastrointestinal, and testis organs. According to the present review, simultaneous consumption of curcumin and CS can attenuate CS toxicities including chronic obstructive pulmonary disease, gastrointestinal toxicity, metabolic diseases, testis injury, and neurotoxicity. Moreover, curcumin suppresses carcinogenesis in the skin, liver, lungs, breast, colon, and stomach. Curcumin mediates these protective effects through antioxidant, anti-inflammatory, anti-apoptotic, and anti-carcinogenicity properties.

Osthole attenuated cytotoxicity induced by 6-OHDA in SH-SY5Y cells through inhibition of JAK/STAT and MAPK pathways.

Objectives: Natural coumarin called osthole is regarded as a medicinal herb with widespread applications in Traditional Chinese Medicine. It has various pharmacological properties, including antioxidant, anti-inflammatory, and anti-apoptotic effects. In some neurodegenerative diseases, osthole also shows neuroprotective properties. In this study, we explored how osthole protects human neuroblastoma SH-SY5Y cells from the cytotoxicity of 6-hydroxydopamine (6-OHDA). Materials and Methods: Using the MTT assay and DCFH-DA methods, respectively, the viability of the cells and the quantity of intracellular reactive oxygen species (ROS) were evaluated. Signal Transducers and Activators of Transcription (STAT), Janus Kinase (JAK), extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and caspase-3 activation levels were examined using western blotting. Results: In SH-SY5Y cells, the results showed that a 24-hour exposure to 6-OHDA (200 µM) lowered cell viability but markedly elevated ROS, p-JAK/JAK, p-STAT/STAT, p-ERK/ERK, p-JNK/JNK ratio, and caspase-3 levels. Interestingly, osthole (100 µM) pretreatment of cells for 24 hr prevented 6-OHDA-induced cytotoxicity by undoing all effects of 6-OHDA. Conclusion: In summary, our data showed that osthole protects SH-SY5Y cells against 6-OHDA-induced cytotoxicity by inhibiting ROS generation and reducing the activity of the JAK/STAT, MAPK, and apoptotic pathways.

A review of therapeutic potentials of milk thistle (Silybum marianum L.) and its main constituent, silymarin, on cancer, and their related patents.

For more than 2000 years, Silybum marianum L. (milk thistle) has been used for treating different complications such as jaundice, hepatitis, and cancers. It has also been shown that silymarin, a flavonolignan extract of the plant, demonstrates chemopreventive effects against cancers. This patent review presents and discusses recent patents concerning the anticancer effects of S. marianum and silymarin. The data were gathered by searching an extensive literature review conducted in Google Scholar, PubMed, Scopus, Google Patent, Patent Scope, and US Patent. Milk thistle and silymarin have been used in a variety of medical, therapeutic, and pharmaceutical fields, according to a large number of documents and patents. Milk thistle and silymarin have been used as complementary treatments for cancers such as skin, prostate, and colorectal cancers, as well as hepatoprotective agents. Silymarin exerts a chemopreventive effect on reactivating cell death pathways by modulation of the antiapoptotic proteins and synergizing with agonists of death domain receptors. Based on the results of these patents, silymarin could be beneficial to oncology patients, especially for the treatment of the side effects of anticancer chemotherapeutics. Following the human propensity to use phytocompounds rather than medicines based on chemical constituents, special attention must be paid to tie the value of milk thistle and silymarin from basic science to clinical applications.

A review of the effects of Urtica dioica (nettle) in metabolic syndrome.

Metabolic syndrome is a serious health condition, yet a common worldwide disorder. It includes several risk factors such as hypertension, dyslipidemia, and high glucose levels which lead the patients to higher risks of cardiovascular diseases, diabetes, and stroke. Phytotherapy plays an important role in treating components of metabolic syndrome. Nettle (Urtica dioica) is considered a valuable plant due to bioactive compounds such as formic acid and rich sources of flavonoids. To acknowledge the role of nettle in metabolic syndrome, several mechanisms have been suggested such as alterations in potassium and calcium channels which improve hypertension. Antihyperlipidemic properties of nettle are mediated by inhibition of HMGCoA reductase and amelioration of lipid peroxidation via antioxidant effects. Also, one of the flavonoids in nettle, quercetin, is responsible for decreasing total cholesterol. Moreover, nettle is responsible for anti-diabetic effects through processes such as increasing insulin secretion and proliferation of pancreatic ß-cells. This review aims to gather different studies to confirm the potential efficacy of nettle in metabolic syndrome.

Protective and therapeutic effects of Scutellaria baicalensis and its main active ingredients baicalin and baicalein against natural toxicities and physical hazards: a review of mechanisms.

OBJECTIVES: Scutellaria baicalensis (SB) has been traditionally used to combat a variety of conditions ranging from ischemic heart disease to cancer. The protective effects of SB are due to the action of two main flavonoids baicalin (BA) and baicalein (BE). This paper aimed to provide a narrative review of the protective and antidotal effects of SB and its main constituents against natural toxicities and physical hazards. EVIDENCE ACQUISITION: Scientific databases Medline, Scopus, and Web of Science were thoroughly searched, based on different keywords for in vivo, in vitro and clinical studies which reported protective or therapeutic effects of SB or its constituents in natural and physical toxicities. RESULTS: Numerous studies have reported that treatment with BE, BA, or total SB extract prevents or counteracts the detrimental toxic effects of various natural compounds and physical hazards. The toxic agents include mycotoxins, lipopolysaccharide, multiple plants and animal-derived substances as well as physical factors which negatively affected vital organs such as CNS, liver, kidneys, lung and heart. Increasing the expression of radical scavenging enzymes and glutathione content as well as inhibition of pro-inflammatory cytokines and pro-apoptotic mediators were important mechanisms of action. CONCLUSION: Different studies on the Chinese skullcap have exhibited that its total root extract, BA or BE can act as potential antidotes or protective agents against the damage induced by natural toxins and physical factors by alleviating oxidative stress and inflammation. However, the scarcity of high-quality clinical evidence means that further clinical studies are required to reach a more definitive conclusion.

Scutellaria baicalensis and its constituents baicalin and baicalein as antidotes or protective agents against chemical toxicities: a comprehensive review.

Scutellaria baicalensis (SB), also known as the Chinese skullcap, has a long history of being used in Chinese medicine to treat a variety of conditions ranging from microbial infections to metabolic syndrome and malignancies. Numerous studies have reported that treatment with total SB extract or two main flavonoids found in its root and leaves, baicalin (BA) and baicalein (BE), can prevent or alleviate the detrimental toxic effects of exposure to various chemical compounds. It has been shown that BA and BE are generally behind the protective effects of SB against toxicants. This paper aimed to review the protective and therapeutic effects of SB and its main components BA and BE against chemical compounds that can cause intoxication after acute or chronic exposure and seriously affect different vital organs including the brain, heart, liver, and kidneys. In this review paper, we had a look into a total of 221 in vitro and in vivo studies from 1995 to 2021 from the scientific databases PubMed, Scopus, and Web of Science which reported protective or therapeutic effects of BA, BE, or SB against drugs and chemicals that one might be exposed to on a professional or accidental basis and compounds that are primarily used to simulate disease models. In conclusion, the protective effects of SB and its flavonoids can be mainly attributed to increase in antioxidants enzymes, inhibition of lipid peroxidation, reduction of inflammatory cytokines, and suppression of apoptosis pathway.

Effects of alpha lipoic acid on metabolic syndrome: A comprehensive review.

Metabolic syndrome (MetS) is a multifactorial disease with medical conditions such as hypertension, diabetes, obesity, dyslipidemia, and insulin resistance. Alpha-lipoic acid (α-LA) possesses various pharmacological effects, including antidiabetic, antiobesity, hypotensive, and hypolipidemia actions. It exhibits reactive oxygen species scavenger properties against oxidation and age-related inflammation and refines MetS components. Also, α-LA activates the 5' adenosine monophosphate-activated protein kinase and inhibits the NFκb. It can decrease cholesterol biosynthesis, fatty acid ß-oxidation, and vascular stiffness. α-LA decreases lipogenesis, cholesterol biosynthesis, low-density lipoprotein and very low-density lipoprotein levels, and atherosclerosis. Moreover, α-LA increases insulin secretion, glucose transport, and insulin sensitivity. These changes occur via PI3K/Akt activation. On the other hand, α-LA treats central obesity by increasing adiponectin levels and mitochondrial biogenesis and can reduce food intake mainly by SIRT1 stimulation. In this review, the most relevant articles have been discussed to determine the effects of α-LA on different components of MetS with a special focus on different molecular mechanisms behind these effects. This review exhibits the potential properties of α-LA in managing MetS; however, high-quality studies are needed to confirm the clinical efficacy of α-LA.

The genus Glycyrrhiza (Fabaceae family) and its active constituents as protective agents against natural or chemical toxicities.

Licorice is the dried roots and rhizomes of various species of the genus Glycyrrhiza (Fabaceae) that have been used in folk medicine from ancient times. Many important research projects have established several beneficial effects for this medicinal herb, including antiinflammatory, antimicrobial, antiviral, antiprotozoal, antioxidant, antihyperglycemic, antihyperlipidemic, hepatoprotective, and neuroprotective. Licorice contains important bioactive components, such as glycyrrhizin (glycyrrhizic, glycyrrhizinic acid), liquiritigenin, liquiritin, and glycyrrhetinic acid. The protective effects of licorice and its main chemical components against toxins and toxicants in several organs including the brain, heart, liver, kidney, and lung have been shown. In this comprehensive review article, the protective effects of these constituents against natural, industrial, environmental, and chemical toxicities with attention on the cellular and molecular mechanism are introduced. Also, it has been revealed that this plant and its main compounds can inhibit the toxicity of different toxins by the antioxidant, antiinflammatory, and anti-apoptotic properties as well as the modulation of Inhibitor of kappaB kinase (IKK), Extracellular signal-regulated protein kinase1/2 (ERK1/2), p38, inducible nitric oxide synthase, and nuclear factor-κB (NF-κB) signaling pathways. More high-quality investigations in both experimental and clinical studies need to firmly establish the efficacy of licorice and its main constituents against toxic agents.

An updated review of protective effects of rosemary and its active constituents against natural and chemical toxicities.

Natural and chemical toxic agents cause severe adverse effects on people's health in a variety of exposing ways. Herbal medications have taken into consideration as alternative safe treatments for toxicities. Rosmarinus officinalis also known as rosemary belongs to the Lamiaceae family. Rosemary and its constituents including carnosic acid, rosmarinic acid, and carnosol have a lot of benefits such as anti-inflammatory, antioxidant, anti-mutagenic, anti-bacterial, antiviral, antinociceptive, and neuroprotective activities. In this literate review, we focused on the protective effects of rosemary and its main compounds against natural and chemical toxicities in both in vitro and in vivo studies. The protective effects of rosemary and its components are mostly mediated through different mechanisms such as the inhibition of oxidative stress, reduction of inflammatory mediators including tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-17 (IL-17), cyclooxygenase-2 (COX-2) and nuclear factor ĸB (NF-ĸB) as well as the modulation of apoptosis and mitogen-activated protein kinase (MAPK) signaling pathways.

Evaluation of the effect of thymoquinone in d-galactose-induced memory impairments in rats: Role of MAPK, oxidative stress, and neuroinflammation pathways and telomere length.

D-galactose (d-gal) induces aging and memory impairment via oxidative stress and neuroinflammation pathways. This study evaluated the neuroprotective activity of thymoquinone (TQ) against d-gal. d-gal (400 mg/kg, SC), d-gal plus TQ (2.5, 5, 10 mg/kg, i.p.), and TQ alone (2.5 and 10 mg/kg) for 8 weeks were administered to rats. The effect of TQ on learning and memory were studied using the Morris water maze test. Malondialdehyde (MDA) and glutathione (GSH) levels were determined in the hippocampus. The levels of MAPKs (p-ERK/ERK, p-P38/P38), cAMP response elements binding (p-CREB/CREB), advanced glycation end products (AGEs), inflammatory markers (TNFα, IL-1ß), glial fibrillary acidic protein (GFAP), and brain-derived neurotrophic factor (BDNF) were analyzed by western blotting. Telomere length was evaluated using real-time PCR. Memory and learning impairment, MDA enhancement, GSH reduction, and neuroinflammation via increasing the TNFα, IL-1ß, and GFAP contents were observed in d-gal group. TQ with d-gal, improved memory impairment, reduced oxidative stress, and alleviated neuroinflammation. The elevated level of AGEs decreased by TQ compared to d-gal. No changes were observed in the levels of p-ERK/ERK, p-CREB/CREB, p-P38/P38, BDNF, and telomere length following administration of d-gal or TQ plus d-gal. TQ improved memory deficits of d-gal through anti-oxidative and anti-inflammatory mechanisms.

Protective effect of punicalagin, the main polyphenol compound of pomegranate, against acrylamide-induced neurotoxicity and hepatotoxicity in rats.

Acrylamide (ACR) is widely used in industries. Oxidative stress and apoptosis pathways are important mechanisms behind ACR-induced hepatotoxicity and neurotoxicity. Regarding to antioxidant and antiapoptotic properties of punicalagin (PUN), the protective effect of this agent on ACR-induced toxicity in rat was evaluated. Rats were divided into seven groups: control, ACR (50 mg/kg/day, i.p.), PUN (10, 20, and 40 mg/kg/day, i.p.) plus ACR, vitamin E (200 mg/kg, i.p.) plus ACR, and PUN groups. After 11 days, the gait score test was evaluated. Then, the animals were sacrificed and the malondialdehyde (MDA) and glutathione (GSH) contents were determined in the brain and liver tissues. Apoptosis-involved factors and myelin basic protein (MBP) were determined by western blotting. Severe movement disorder, MDA enhancement, and GSH reduction in the brain and liver tissues were observed in ACR-treated animals. The Bax/Bcl2 ratio and caspase-3 levels were enhanced in the tested tissues. ACR elevated the level of aspartate aminotransferases and decreased serum protein and albumin concentration. PUN recovered movement disorders, changed the level of markers which are important in oxidative stress and reduced apoptosis. Also, PUN increased the MBP level which was reduced due to ACR toxicity. PUN can protect against ACR-induced toxicity through antioxidant and antiapoptotic properties.

Protective effects of Vitis vinifera (grapes) and one of its biologically active constituents, resveratrol, against natural and chemical toxicities: A comprehensive review.

Vitis vinifera (grape) is one of the "most-produced fruit" in the world. Grape seeds are a valuable source of phenolic compounds including resveratrol (RSV). Grape and one of its biologically active constituents, RSV, exert their protective effects against different natural or chemical toxins which could alter physiological homeostasis through a variety of mechanisms. Some of these mechanisms of actions include increase in superoxide dismutase, hemeoxygenase-1, and glutathione peroxidase activities and reduced glutathione content and decrease in malondialdehyde (MDA) levels and activation of the nuclear erythroid2-related factor2/ARE pathway. There are also various reports of the potential use of such compounds in preventing different ailments including cardiovascular diseases, cancer, degenerative diseases, and inflammatory disorders. Therefore, in this review, we have investigated the possible protective effects of grape and one of its biologically active constituents, RSV, on different organs' toxicity induced by natural toxins (such as mycotoxins, lipopolysaccharide, and triptolide) and chemical toxins (such as antitumors, metals, and carbon tetrachloride). There are insufficient clinical trials on this subject, so our review only includes in vivo and in vitro studies. To establish the grape beneficial effects in human intoxication, more clinical trials need to be accomplished.

Rosmarinic acid attenuates development and existing pain in a rat model of neuropathic pain: An evidence of anti-oxidative and anti-inflammatory effects.

BACKGROUND: We aimed to investigate the potential prophylactic and curative effects of rosmarinic acid, one of the main constituents of rosemary, on the neuropathic pain induced by chronic constriction injury (CCI) in rats. MATERIALS AND METHODS: CCI was used to induce peripheral neuropathic pain. In prophylactic groups, rosmarinic acid (10, 20, and 40 mg/kg, i.p.) was administered from the day of surgery (day 0) for 14 days. In treatment group, rosmarinic acid (40 mg/kg) was given from day 5 (after the pain was established), for 7 days. The degree of mechanical allodynia, cold allodynia, and heat hyperalgesia were measured on days 0, 3, 5, 7, 10 and 14 post-surgery. The open field test was carried out to assess locomotor activity of animals. Lumbar spinal cord levels of astroglia activation marker, glial fibrillary acidic protein (GFAP), microglial activation marker, ionized calcium-binding adapter molecule 1 (Iba-1), toll-like receptor 4 (TLR-4), tumor necrosis factor alpha (TNF-α), inducible isoform of nitric oxide synthase enzyme (iNOS) and apoptotic factors were quantified via western blot on days 7 and 14. RESULTS: CCI rats showed a significant mechanical allodynia, cold allodynia and thermal hyperalgesia, compared to sham ones on day 3, persisted up to day 14 post-CCI. Rosmarinic acid was able to prevent and also attenuate CCI-induced behavioral features in prophylactic as well as treatment groups, respectively. A significant increase in the levels of TNF-α, iNOS, apoptotic factors (Bax, caspases 3, 9), Iba-1, TLR-4, and GFAP was observed on both days 7 and 14, which was suppressed by 14 days administration of rosmarinic acid. CONCLUSION: These findings further support the use of rosemary in traditional medicine to alleviate pain. Rosmarinic acid could be a promising compound in prophylaxis and treatment of neuropathic pain. Anti-apoptotic and anti-inflammatory effects of rosmarinic acid may have important roles in the observed antinociceptive properties.

Protective effect of crocin on BPA-induced liver toxicity in rats through inhibition of oxidative stress and downregulation of MAPK and MAPKAP signaling pathway and miRNA-122 expression.

Bisphenol A (BPA) is an artificial environmental endocrine disrupting chemical and commonly used as a monomer of polycarbonate plastics and epoxy resins. The aim of the present study is to investigate the hepatoprotective effects of crocin, a constituent of saffron, against BPA-induced liver toxicity. We showed that treatment of male Wistar rats with 0.5 mg/kg BPA for 30 days increased the level of 8-isoprostane, decreased the level of reduced glutathione, elevated serum levels of aspartate aminotransferase, lactate dehydrogenase, triglyceride, and glucose, and induced periportal inflammation. Western blot results revealed that BPA increased the phosphorylation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase (ERK1/2), and mitogen-activated protein kinase-activated protein kinase (MAPKAPK), but not p38. BPA also reduced the Akt signaling activation and upregulated microRNA (miR-122) expression. Moreover, we showed here that crocin 20 mg/kg administration ameliorated liver damage and improved elevated levels of TG and liver enzymes of BPA-treated rats possibly though antioxidant activity, downregulation of miR-122 transcript level and lowering the phosphorylation of JNK, ERK1/2, and MAPKAPK and subsequently their activities. Overall, the findings suggest that crocin possesses hepatoprotective effects against BPA-induced liver toxicity by enhancing the antioxidative defense system and regulation of important signaling pathway activities and miR-122 expression.

Berberis vulgaris and its constituent berberine as antidotes and protective agents against natural or chemical toxicities.

Berberis vulgaris L (B. vulgaris) and its main constituent berberine have been used in traditional medicine for a long time. This medicinal plant and berberine have many properties that have attracted the attention of researchers over the time. According to several studies, B. vulgaris and berberine exhibited anti-inflammatory, antioxidant, anticonvulsant, antidepressant, anti-Alzheimer, anti-cancer, anti-arrhythmic, antiviral, antibacterial and anti-diabetic effects in both in vitro and invivo experiments. In regard to many reports on protective effects of B. vulgaris and berberine on natural and chemical toxins, in the current review article, the inhibitory effects of these compounds against natural, industrial, environmental and chemical toxicities with focus on cellular mechanism have been categorized. It has been mentioned that berberine could ameliorate toxicity of chemical toxins in brain, heart, kidney, liver and lung in part through antioxidant, anti-inflammatory, anti-apoptotic, modulation of mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways.

Toxicology effects of saffron and its constituents: a review.

Saffron (Crocus sativus L.) has been considered as a medicinal plant since ancient times and also widely used as food additive for its color, taste and odor. The pharmacological properties of saffron and its main constituents, crocin and safranal have been evaluated using different in vivo and in vitro models. Additionally, other lines of studies have found toxicological effects of saffron. However, a comprehensive review that covers all aspects of its toxicity has not been published yet. The current study provides classified information about the toxic effects of saffron and its constituents in various exposure conditions including acute, sub-acute, sub-chronic and chronic studies. Therapeutic doses of saffron exhibits no significant toxicity in both clinical and experimental investigations.

Anti-inflammatory effects of ethanolic extract of Rosmarinus officinalis L. and rosmarinic acid in a rat model of neuropathic pain.

BACKGROUND: Rosemary, Rosmarinus (R.) officinalis L. is a well-known plant with several useful properties such as analgesic, anti-inflammatory and anti-neurodegenerative. It has been used in folk medicine to alleviate rheumatic pain, stomachache and dysmenorrhea. Rosemary has several constituents such as rosmarinic acid which can be responsible for therapeutic properties been noted with rosemary. The aim of this study was to investigate the potential anti-inflammatory effects of R. officinalis and rosmarinic acid in a rat model of sciatic nerve chronic constriction injury (CCI)-induced neuropathic pain to verify usage of rosemary in folk medicine. METHODS: Rats underwent CCI, were treated with either normal saline, ethanolic extract of aerial parts of R. officinalis (400mg/kg, i.p.) or rosmarinic acid (40mg/kg, i.p.) from the day of surgery (day 0) for 14days. The anti-inflammatory effects of R. officinalis extract and rosmarinic acid were evaluated by assessing the levels of some spinal inflammatory markers including cyclooxygenase-2 (COX2), prostaglandin E2 (PGE-2), interleukin 1 beta (IL-1ß), matrix metallopeptidase 2 (MMP2) through western blotting and nitric oxide (NO) production via Griess reaction on days 7 and 14 post-surgery. RESULTS: CCI rats exhibited a marked expression in the levels of inflammatory markers (COX2, PGE-2, IL-1ß, MMP2 and NO) on both days 7 (p<0.001) and 14 (p<0.001). Rosmarinic acid and ethanolic extract of R. officinalis were able to decrease amounts of mentioned inflammatory markers on both days 7 (p<0.001) and 14 (p<0.001). CONCLUSION: Our data support the traditional use of R. officinalis as an effective remedy for pain relief and inflammatory disorders. It also suggests that the ethanolic extract of R. officinalis and rosmarinic acid through modulating neuro-inflammation might be potential candidates in treating neuropathic pain and different neurological disorders associated with inflammation.

Memory enhancement and protective effects of crocin against D-galactose aging model in the hippocampus of Wistar rats.

OBJECTIVES: The neurodegeneration and loss of memory function are common consequences of aging. Medicinal plants have potent protective effects against chronic neurodegenerative diseases. The aim of this study was to investigate the beneficial effects and molecular mechanisms of crocin on brain function in D-galactose (D-gal)-induced aging model in rats. MATERIALS AND METHODS: Male Wistar rats weighing 220 ± 20 g were randomly divided into six groups: control, D-gal (400 mg/kg, SC), D-gal (400 mg/kg) plus crocin (7.5, 15, 30 mg/kg, IP) and crocin alone at dose of 30 mg/kg for 8 weeks. The neuroprotective effects of crocin were evaluated by Morris water maze, determination of malondialdehyde (MDA) levels and Western blot analysis. RESULTS: Crocin significantly inhibited the neurotoxic effects of D-gal through improvement of spatial learning and memory functions as well as the reduction of MDA levels. It was also found that administration of crocin up-regulated pAkt/Akt and pErk/Erk ratio which were decreased by chronic D-gal treatment. In addition, the elevated level of carboxymethyl lysine (CML), as an advance glycation product (AGE), NF-κB p65, TNFα and IL1ß significantly decreased in crocin treated rats compared to D-gal group. CONCLUSION: These findings suggest that crocin is able to enhance memory function in D-gal aging model through anti-glycative and anti-oxidative properties which finally can suppress brain inflammatory mediators (IL-1, TNF and NF-κB) formations and increase PI3K/Akt and Erk/MAPK pathways activity. Therefore, crocin can be considered as healthcare product to prevent age-related brain diseases such as Alzheimer.

Effect of alcoholic extract of aerial parts of Rosmarinus officinalis L. on pain, inflammation and apoptosis induced by chronic constriction injury (CCI) model of neuropathic pain in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: According to traditional medicine, rosemary (Rosmarinus officinalis) has been used in many ailments such as dysmenorrhea, rheumatic pain and stomachache. AIM OF THE STUDY: This work was carried out to evaluate putative anti-allodynic and anti-hyperalgesic effects of Rosmarinus officinalis alcoholic extract and some spinal cord molecular changes on a neuropathic pain model in rats. MATERIALS AND METHODS: Peripheral neuropathy was induced by chronic constriction injury (CCI) of sciatic nerve. Rats were treated daily with alcoholic extract of aerial parts of R. officinalis (100, 200, and 400mg/kg, i.p.), from the day of surgery (day 0) for 14 days. Mechanical allodynia, cold allodynia and heat hyperalgesia were measured on days 0, 3, 5, 7, 10 and 14. Investigations into mechanisms involved measurement of apoptotic factors (bcl-2-like protein (Bax)), cleaved caspases 3 and 9, anti-apoptotic mediator, Bcl2, inflammatory mediators including tumor necrosis factor alpha (TNF-α), inducible isoform of nitric oxide synthase (iNOS), toll like receptor 4 (TLR4), microglial activation marker, ionized calcium-binding adapter molecule 1 (Iba-1) and astroglia activation marker, glial fibrillary acidic protein (GFAP) were measured via western blot on days 7 and 14. RESULTS: CCI rats exhibited a marked mechanical allodynia, cold allodynia, and thermal hyperalgesia on days 3, 5, 7, 10, and 14 post-CCI. All three doses of rosemary alcoholic extract were able to attenuate neuropathic behavioral changes as compared with CCI animals that received vehicle. In the vehicle-treated CCI group, a significant increase in levels of Bax, cleaved caspases 3 and 9, Iba1, TNF-α, iNOS and TLR4 levels was detected on both days 7 and 14. Rosemary extract, 400mg/kg significantly decreased the amounts of mentioned apoptotic, inflammatory and glial markers as compared with vehicle-treated CCI animals. CONCLUSIONS: Anti-inflammatory and anti-apoptotic processes might contribute to the anti-allodynic and anti-hyperalgesic effects of rosemary following nerve injury. Our findings support the ethnopharmacological use of rosemary as a potential candidate in treating neuropathic pain and different neurological disorders that associate with the activation of apoptosis and inflammatory pathways.