Wood calamint ameliorates ethanol-induced stomach injury in rats by augmentation of hsp/bax and inflammatory mechanisms.

Clinopodium menthifolium (wood calamint) is a folkloric medicinal plant ingested as a treatment for many human disorders including gastric disorders. Our study evaluates the anti-ulcer potentials of Clinopodium menthifolium ethanol extracts (CMEE) in induced gastric ulcers in rats. Thirty Dawley male rats were divided into 5 groups: normal and ulcer controls, treated orally with Tween 20%; reference rats treated with Omeprazole 20 mg/kg, and the remaining two groups received 250 and 500 mg/kg CMEE for 2 weeks. After that, food was taken away for 24 h, and then, rats received ethanol-induced gastric ulceration (except normal control), 80% (1 ml/rat). After anesthetization and sacrificing, the ulcer index, mucus content, and other ulcer measurements were obtained from dissected rat stomachs. Stomach tissues were also analyzed by different histology procedures and homogenized stomach tissues were assessed for their antioxidant contents. The toxicity trial showed the absence of any toxic signs in rats supplemented with 2 and 5 g/kg of CMEE. The gastroprotective results showed a significantly lower ulcer index and higher gastric mucin content in CMEE-ingested rats compared to ulcer controls. Furthermore, CMEE treatments significantly increased the intensity of periodic acid Schiff stained (PAS), HSP 70 protein, and down-regulation of Bax protein expression in the stomach epithelium. Rats supplemented with 500 mg/kg revealed noticeable changes in their serum inflammatory cytokines along with positive regulations of antioxidant enzymes. The outcomes provide a scientific backup behind the gastroprotective potential effect of CMEE that could serve as a natural resource against peptic ulcers.

Cumin (Cuminum cyminum L.) seeds accelerates wound healing in rats: Possible molecular mechanisms.

Wound healing is a complex, intricate, and dynamic process that requires effective therapeutic management. The current study evaluates the wound healing potentials of methanolic extract of Cuminum cyminum L. seeds (CCS) in rats. Sprague Dawley (24) rats were distributed into four cages, wounds produced on the back of the neck, and received two daily topical treatments for 14 days: A, rats received normal saline; B, wounded rats treated with intrasite gel; C and D, rats received 0.2 mL of 250 and 500 mg/kg of CCS, respectively. After that, wound area and closure percentage were evaluated, and wound tissues were dissected for histopathological, immunohistochemical, and biochemical examinations. Acute toxicity trials of methanolic extract of CCS showed the absence of any physiological changes or mortality in rats. CCS application caused a significant reduction in wound size and a statistically elevated percentage of wound contraction than those of vehicle rats. CCS treatment caused significant up-regulation of collagen fiber, fibroblasts, and fewer inflammatory cells (inflammation) in granulation tissues. TGF-ß1 (angiogenetic factor) was significantly more expressed in CCS-treated rats in comparison to normal saline-treated rats; therefore, more fibroblasts transformed into myofibroblasts (angiogenesis). CCS-treated rats showed remarkable antioxidant potentials (higher SOD and CAT enzymes) and decreased MDA (lipid peroxidation) levels in their wound tissue homogenates. Hydroxyproline amino acid (collagen) was significantly up-regulated by CCS treatment, which is commonly related to faster wound closure area. The outcomes suggest CCS as a viable new source of pharmaceuticals for wound treatment.

Mangiferin (mango) attenuates AOM-induced colorectal cancer in rat's colon by augmentation of apoptotic proteins and antioxidant mechanisms.

Mangiferin (MF) is a natural C-glucosylxantone compound that has many substantial curative potentials against numerous illnesses including cancers. The present study's goal is to appraise the chemo preventive possessions of MF on azoxymethane (AOM)-mediated colonic aberrant crypt foci (ACF) in rats. Rats clustered into 5 groups, negative control (A), inoculated subcutaneously with normal saline twice and nourished on 0.5% CMC; groups B-E injected twice with 15 mg/kg azoxymethane followed by ingestion of 0.5% CMC (B, cancer control); intraperitoneal inoculation of 35 mg/kg 5-fluorouracil (C, reference rats) or nourished on 30 mg/kg (D) and 60 mg/kg (E) of MF. Results of gross morphology of colorectal specimens showed significantly lower total colonic ACF incidence in MF-treated rats than that of cancer controls. The colon tissue examination of cancer control rats showed increased ACF availability with bizarrely elongated nuclei, stratified cells, and higher depletion of the submucosal glands compared to MF-treated rats. Mangiferin treatment caused increased regulation of pro-apoptotic (increased Bax) proteins and reduced the ß-catenin) proteins expression. Moreover, rats fed on MF had significantly higher glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase (CAT), and lower malondialdehyde (MDA) concentrations in their colonic tissue homogenates. Mangiferin supplementation significantly down-shifted pro-inflammatory cytokines (transforming growth factor-α and interleukine-6) and up-shifted anti-inflammatory cytokines (interleukine-10) based on serum analysis. The chemo-protective mechanistic of MF against AOM-induced ACF, shown by lower ACF values and colon tissue penetration, could be correlated with its positive modulation of apoptotic cascade, antioxidant enzymes, and inflammatory cytokines originating from AOM oxidative stress insults.

Sinomenine accelerate wound healing in rats by augmentation of antioxidant, anti-inflammatory, immunuhistochemical pathways.

Sinomenine (SN) is a well-documented unique plant alkaloid extracted from many herbal medicines. The present study evaluates the wound healing potentials of SN on dorsal neck injury in rats. A uniform cut was created on Sprague Dawley rats (24) which were arbitrarily aligned into 4 groups receiving two daily topical treatments for 14 days as follows: A, rats had gum acacia; B, rats addressed with intrasite gel; C and D, rats had 30 and 60 mg/ml of SN, respectively. The acute toxicity trial revealed the absence of any toxic signs in rats after two weeks of ingestion of 30 and 300 mg/kg of SN. SN-treated rats showed smaller wound areas and higher wound closure percentages compared to vehicle rats after 5, 10, and 15 days of skin excision. Histological evaluation of recovered wound tissues showed increased collagen deposition, fibroblast content, and decreased inflammatory cells in granulated tissues in SN-addressed rats, which were statistically different from that of gum acacia-treated rats. SN treatment caused positive augmentation of Transforming Growth Factor Beta 1 (angiogenetic factor) in wound tissues, denoting a higher conversion rate of fibroblast into myofibroblast (angiogenesis) that results in faster wound healing action. Increased antioxidant enzymes (SOD and CAT), as well as decreased MDA contents in recovered wound tissues of SN-treated rats, suggest the antioxidant potentials of SN that aid in faster wound recovery. Wound tissue homogenates showed higher hydroxyproline amino acid (collagen content) values in SN-treated rats than in vehicle rats. SN treatment suppressed the production of pro-inflammatory cytokines and increased anti-inflammatory cytokines in the serum of wounded rats. The outcomes present SN as a viable pharmaceutical agent for wound healing evidenced by its positive modulation of the antioxidant, immunohistochemically proteins, hydroxyproline, and anti-inflammatory cytokines.

Pinostrobin attenuates azoxymethane-induced colorectal cytotoxicity in rats through augmentation of apoptotic Bax/Bcl-2 proteins and antioxidants.

Objectives: Pinostrobin (5-hydroxy-7-methoxyflavanone; PN) is a natural active ingredient with numerous biological activities extensively utilized in tumour chemotherapy. The present study investigates the chemo-preventive potentials of PN on azoxymethane-mediated colonic aberrant crypt foci in rats. Methods: Sprague Dawley rats clustered into five groups, normal control (A) and cancer controls were subcutaneously injected with normal saline and 15 mg/kg azoxymethane, respectively, and nourished on 10% tween 20 and fed on 10% tween 20; reference control (C), injected with 15 mg/kg azoxymethane and injected (intraperitoneal) with 35 mg/kg 5-fluorouracil (5-FU); D and E rat groups received a subcutaneous injection of 15 mg/kg azoxymethane and nourished on 30 and 60 mg/kg of PN, respectively. Results: The acute toxicity trial showed a lack of any abnormal signs or mortality in rats ingested with 250 and 500 mg/kg of PN. The gross morphology of colon tissues revealed significantly lower total colonic aberrant crypt foci incidence in PN-treated rats than that of cancer controls. Histological examination of colon tissues showed increased aberrant crypt foci availability with bizarrely elongated nuclei, stratified cells and higher depletion of the submucosal glands in cancer controls. PN treatment caused positive modulation of apoptotic (Bax and Bcl-2) proteins and inflammatory cytokines (TNF-α, IL-6 and IL-10). Moreover, rats fed on PN had significantly higher antioxidants (superoxide dismutase) and lower malondialdehyde concentrations in their colon tissue homogenates. Conclusion: The chemoprotective efficiency of PN against azoxymethane-induced aberrant crypt foci is shown by lower aberrant crypt foci values and higher aberrant crypt foci inhibition percentage, possibly through augmentation of genes responsible for apoptotic cascade and inflammations originating from azoxymethane oxidative stress insults.

Hepatoprotective Effects of Biochanin A on Thioacetamide-Induced Liver Cirrhosis in Experimental Rats.

The protective effect of biochanin A (BCA) on the histopathology, immunohistochemistry, and biochemistry of thioacetamide (TAA)-induced liver cirrhosis in vivo was investigated. There was a significant reduction in liver weight and hepatocyte propagation, with much lower cell injury in rat groups treated with BCA (25 mg/kg and 50 mg/kg) following a TAA induction. These groups had significantly lower levels of proliferating cell nuclear antigen (PCNA) and α-smooth muscle actin (α-SMA). The liver homogenates showed increased antioxidant enzyme activity of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), as well as decreased malondialdehyde (MDA) levels. The serum biomarkers associated with liver function, namely alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transaminase (GGT), returned to normal levels, comparable to those observed in both the normal control group and the reference control group. Taken together, the normal microanatomy of hepatocytes, the inhibition of PCNA and α-SMA, improved antioxidant enzymes (SOD, CAT, and GPx), and condensed MDA with repairs of liver biomarkers validated BCA's hepatoprotective effect.

Hepatoprotective effects of Gynura procumbens against thioacetamide-induced cirrhosis in rats: Targeting inflammatory and oxidative stress signalling pathways.

Gynura procumbens is an edible flowering plant that has been utilized as traditional therapy for numerous diseases. The current experiment investigates the hepatoprotective potentials of the ethanol extract of Gynura procumbens leaf (EEGPL) against thioacetamide (TAA)-induced liver cirrhosis in rats. Thirty Sprague Dawley rats were randomly divided into 5 clusters: A, rats received orally 10% Tween 80 and intraperitoneal (i.p) inoculation of sterile distal water; B, rats received orally10% Tween 80; C, rats received orally daily 50 mg/kg of silymarin, while groups; D and E, rats received orally daily doses of 200 and 400 mg/kg of EEGPL, respectively. Furthermore, B-E clusters received 200 mg/kg thioacetamide (i.p) three times a week for 60 days. The liver gross morphology of rats that received only TAA (B) revealed irregular rough surface layers compared to smoother livers of rats that received EEGPL. Histopathology of group B revealed clear hepatic necrosis and fibrous connective tissue, which were significantly reduced in C-E groups. EEGPL treatment caused a significant down-regulation of PCNA and α-SMA protein expressions. Antioxidant (SOD and CAT) enzymes in hepatic homogeneity were meaningfully lower, and MDA levels were significantly higher in TAA controls compared to those of C-E groups. Moreover, EEGPL treatment caused a reduction of TNF-α and IL-6 and increased expression of IL-10 cytokines. Therefore, the hepatoprotective potentials of EEGPL might be contributed to its modulation of detoxification enzymes, anti-inflammatory, and antioxidant activities.

Boric Acid (Boron) Attenuates AOM-Induced Colorectal Cancer in Rats by Augmentation of Apoptotic and Antioxidant Mechanisms.

Boric acid (BA) is a naturally occurring weak Lewis acid containing boron, oxygen, and hydrogen elements that can be found in water, soil, and plants. Because of its numerous biological potentials including anti-proliferation actions, the present investigates the chemopreventive possessions of BA on azoxymethane (AOM)-induced colonic aberrant crypt foci (ACF) in rats. Thirty laboratory rats were divided into 5 groups: negative control (A) received two subcutaneous inoculations of normal saline and nourished on 10% Tween 20; groups B-E had two injections of 15 mg/kg azoxymethane followed by ingestion of 10% Tween 20 (B, cancer control), inoculation with intraperitoneal 35 mg/kg 5-fluorouracil injection (C, reference group), or ingested with boric acid 30 mg/kg (D) and 60 mg/kg (E). The gross morphology results showed significantly increased total colonic ACF in cancer controls, while BA treatment caused a significant reduction of ACF values. Histopathological evaluation of colons from cancer controls showed bizarrely elongated nuclei, stratified cells, and higher depletion of the submucosal glands than that of BA-treated groups. Boric acid treatment up-surged the pro-apoptotic (Bax) expression and reduced anti-apoptotic (Bcl-2) protein expressions. Moreover, BA ingestion caused upregulation of antioxidant enzymes (GPx, SOD, CAT), and lowered MDA contents in colon tissue homogenates. Boric acid-treated rats had significantly lower pro-inflammatory cytokines (TNF-α and IL-6) and higher anti-inflammatory cytokines (IL-10) based on serum analysis. The colorectal cancer attenuation by BA is shown by the reduced ACF numbers, anticipated by its regulatory potentials on the apoptotic proteins, antioxidants, and inflammatory cytokines originating from AOM-induced oxidative damage.

Gastroprotective effects of Polygonatum odoratum in rodents by regulation of apoptotic proteins and inflammatory cytokines.

In an increasing interest in natural antiulcer compounds that may have gastric healing effects and possibly prevent ulcer recurrence, Polygonatum odoratum appears as a strong candidate. The gastroprotective potentials of P. odoratum rhizome extract (PORE) were explored on ethanol-induced gastric ulceration in rats. Sprague Dawley rats were caged in 5 groups, normal and ulcer control rats received CMC (1% carboxymethyl cellulose). Omeprazole (20 mg/kg) was given to reference Rats. Experimental rats were treated with 250 mg/kg and 500 mg/kg PORE, respectively. After an hour, the normal control rats received 1% CMC, whereas rat groups 2-5 were given absolute ethanol by oral gavage. After 60 min, rats received anesthesia and were sacrificed. Dissected gastric tissue was analyzed by histopathological and immunohistochemical techniques. PORE treatment significantly lowered the ethanol-induced gastric injury, as shown by up-surging gastric pH and mucus content, reduced leukocyte infiltration, lower ulcerative areas in mucosal layers, and increased antioxidants (SOD and CAT) and (MDA) levels. Furthermore, PORE pre-treated rats showed significantly increased expression of the Periodic acid-Schiff (PAS), HSP-70 protein, and decreased Bax protein in their gastric epithelial layers. PORE treatment showed an important regulation of inflammatory cytokines shown by decreasing the TNF-a, and IL-6 and increasing the IL-10 values. The detected biological activity of PORE is encouraging and presents the scientific evidence for its traditional use as a gastroprotection agent however further studies are required to determine the exact phytochemicals and mechanism pathway responsible for this bioactivity.

Sinapic Acid Attenuate Liver Injury by Modulating Antioxidant Activity and Inflammatory Cytokines in Thioacetamide-Induced Liver Cirrhosis in Rats.

Sinapic acid (SA) is a natural pharmacological active compound found in berries, nuts, and cereals. The current study aimed to investigate the protective effects of SA against thioacetamide (TAA) fibrosis in rats by histopathological and immunohistochemical assays. The albino rats (30) were randomly divided into five groups (G). G1 was injected with distilled water 3 times/week and fed orally daily with 10% Tween 20 for two months. G2-5 were injected with 200 mg/kg TAA three times weekly for two months and fed with 10% Tween 20, 50 mg/kg silymarin, 20, and 40 mg/kg of SA daily for 2 months, respectively. The results showed that rats treated with SA had fewer hepatocyte injuries with lower liver index (serum bilirubin, total protein, albumin, and liver enzymes (ALP, ALT, and AST) and were similar to that of control and silymarin-treated rats. Acute toxicity for 2 and 4 g/kg SA showed to be safe without any toxic signs in treated rats. Macroscopic examination showed that hepatotoxic liver had an irregular, rough surface with micro and macro nodules and histopathology expressed by Hematoxylin and Eosin, and Masson Trichrome revealed severe inflammation and infiltration of focal necrosis, fibrosis, lymphocytes, and proliferation bile duct. In contrast, rats fed with SA had significantly lower TAA toxicity in gross and histology and liver tissues as presented by less liver tissue disruption, lesser fibrosis, and minimum in filtered hepatocytes. Immunohistochemistry of rats receiving SA showed significant up-regulation of HSP 70% and down-regulation of alpha-smooth muscle actin (α-SMA) protein expression compared to positive control rats. The homogenized liver tissues showed a notable rise in the antioxidant enzymes (SOD and CAT) actions with significantly lower malondialdehyde (MDA) levels compared to that of the positive control group. Furthermore, the SA-treated rats had significantly lower TNF-a, IL-6, and higher IL-10 levels than the positive control rats. Thus, the findings suggest SA as a hepatoprotective compound due to its inhibitory effects on fibrosis, hepatotoxicity, liver cell proliferation, up-regulation of HSP 70, and downregulation of α-SMA expression, inhibiting lipid peroxidation (MDA), while retaining the liver index and antioxidant enzymes to normal.

Chemopreventive Effects of Onosma mutabilis against Azoxymethane-Induced Colon Cancer in Rats via Amendment of Bax/Bcl-2 and NF-κB Signaling Pathways.

Onosma species (Boraginaceae) are well known as medicinal plants due to their wide range of pharmaceutical potential. The present study aims to investigate the anticancer (in vitro) and chemo-protective (in vivo) efficacies of Onosma mutabilis extract (OME) in the azoxymethane (AOM)-induced aberrant crypt foci (ACF) in rats. The in vitro antiproliferative effects of OME were determined on two human tumor cell lines (Caco-2 and HT-29) via MTT assay. The in vivo chemoprotective effects of OME were investigated by performing various biochemical analyses in serum and tissue homogenates of albino rats, along with determining oxidative stress biomarkers. Inflammatory biomarkers of colon, colonic gross morphology (by methylene blue), ACF formation, and colonic histopathology (H & E stain) were determined. The immunohistochemistry of colonic tissues was also assessed by Bax and Bcl-2 protein expression. The results showed that the antitumor activity of OME against Caco-2 and HT-29 colorectal cancer cells ranged between 22.28-36.55 µg/mL. OME supplementation caused a significant drop in the ACF values and improved the immunohistochemistry of the rats shown by up-regulation of Bax and down-regulation of Bcl-2 protein expressions. These outcomes reveal that O. mutabilis may have chemoprotective efficiency against AOM-induced colon cancer represented by the attenuation of ACF formation possibly through inhibition of free radicals, inflammation, and stimulation of the colon antioxidant armory (SOD, CAT, and GPx) and positive regulation of the Nrf2-Keap1 pathway.

Green Synthesis of Silver Nanoparticles from Aqueous Extract of Tinospora crispa Stems Accelerate Wound Healing in Rats.

GRAPHICAL ABSTRACT: [Formula: see text].

Effect of nano silver on gastroprotective activity against ethanol-induced stomach ulcer in rats.

Silver nanoparticles (Ag NPs) have unique properties and display an important role in bioactivities such as antimicrobial, antiviral, antifungal, and anticancer. Stable Ag NPs were prepared by reaction of silver nitrate solution with extract of Melissa and characterized by UV-Vis spectroscopy, AFM, SEM, XRD, and Zeta potential. The resulted Ag NPs have a size range between 20 and 35 nm. The current study aims to evaluate the gastroprotective effect of Ag NPs against ethanol-induced gastric ulcers in rats. Thirty rats were randomly divided into five groups. The experimental groups were fed 175 and 350 ppm/p.o of Ag NPs orally. Ag NPs improved the adversative influence of ethanol-induced stomach damage as confirmed by declining ulcer index and raised the percentage of ulcer prevention. Significantly reduced ethanol-induced gastric lesions were evidenced by increased mucus secretion and pH of stomach content, decreased ulcer area, nonappearance of edema, and leucocyte penetration of the subcutaneous layer. In gastric homogenate, Ag NPs displayed a substantial upsurge in superoxide dismutase (SOD), catalase (CAT) activities, and significantly reduced malondialdehyde (MDA) levels., Ag NPs increased the intensity of periodic acid Schiff stained (PAS) and produced over-regulation of HSP-70 and down-regulation of Bax proteins. Ag NPs confirmed gastro-protection which might be attributed to its antioxidant effect, increased mucus secretion, increased SOD, and CAT, reduced MDA level, over-regulation of HSP-70 protein, and down-regulation of Bax protein.

In vivo hepatoprotective effect of Morinda elliptica stem extract against liver fibrosis induced by thioacetamide.

Morinda elliptica L. (Rubiaceae) is a phytomedicinal herb, used to treat gastrointestinal complications in Peninsular Malaysia. The study evaluates the in vivo hepatoprotective activity of ethanolic extract of M. elliptica stem in thioacetamide (TAA) induced liver fibrosis in male Sprague Drawly rats. Thirty adult rats were divided into five groups of six rats each. Rats of the normal control group received intraperitoneal injections (i. p.) of vehicle 10% Tween-20, 5 ml/kg, and hepatotoxic group 200 mg/kg TAA three times per week respectively. Three supplementary groups were treated with TAA plus daily oral silymarin (50 mg/kg) or M. elliptica (250 or 500 mg/kg). After 8 weeks of treatment, all rats were sacrificed. Liver fibrosis was assessed by gross macroscopic and microscopic tissue analysis, histopathological, and biochemical analysis. The livers of the TAA treated group showed uniform coarse granules, hepatocytic necrosis with lymphocytes infiltration. Contrary, the livers of M. elliptica treated groups (250 and 500 mg/kg) were much smoother and the cell damage was much lesser. The livers of M. elliptica treated groups rats showed elevated activity of SOD and CAT with a significant decrease in MDA level at p < .0001. The level of liver damage parameters, that is, ALP, ALT, and AST, bilirubin, total protein, and albumin were restored to the normal comparable to silymarin. M. elliptica stem extract significantly promoted normal rat liver architecture with significant perfections in biochemical parameters. The molecular contents of M. elliptica with hepatoprotective influence could be discovered, is the future prospective of this study.

The strategy for controlling COVID-19 in Kurdistan Regional Government (KRG)/Iraq: Identification, epidemiology, transmission, treatment, and recovery.

This study has carried out a mini-review on first wave of COVID-19 infection and its control by the Kurdistan Regional Government (KRG)/Iraq. COVID-19 infection, which was named by the International Committee of Taxonomy of Viruses (ICTV) as SARS-CoV-2, is a newly identified coronavirus. The last century has seen the outbreak of numerous life-threatening human pathogens including Nipah, Ebola, Zika, Chikungunya, Middle East respiratory syndrome coronavirus (MERS-CoV), severe acute respiratory syndrome coronavirus (SARS-CoV), and more recently a novel coronavirus has been observed. COVID-19 infection has so far spread to more than 186 countries around the world and KRG/Iraq has not been free from this virus. In this survey, the control of COVID-19 infection in KRG as a part of Iraq is discussed in detail. The methods of identification as well as the drugs that are currently in common use to reduce the wide distribution of COVID-19 infection and their effects in countries around the world are considered. So far, 714 positive cases have been reported by the ministry of health in Kurdistan Region Government-Iraq (KRG), among which there have been only 8 deaths, and 420 cases have recovered. Those who died had a previous history of a chronic disease such as diabetes, hypertension, heart disease, and hypercholesteremia. Alternative medicine based on natural green methods has been widely used by Kurdish people in past years for treatment of strong coughs. In the present study, some natural products which are cost free and effective in enhancing the body's resistance against the virus are considered. A surprising finding is that the patients in KRG have not in general had a severe cough, flu, or fever. The possible explanation may relate to the patients' strong immune systems, since none of them had a history of using alcohol and drugs, or of chronic disease. The epidemiology and transmission of the virus are discussed as well.

In vivo acute toxicity evaluation and in vitro molecular mechanism study of antiproliferative activity of a novel indole Schiff base ß-diiminato manganeseIII complex in hormone-dependent and triple negative breast cancer cells.

Breast cancer is the most frequently diagnosed cancer among women worldwide. Recently, increasing attention has been paid to the anticancer effects of transition metal complexes of indole Schiff bases. ß-diiminato ManganeseIII complex has shown promising cell cycle arrest and apoptosis induction against MCF-7 and MDA-MB-231 breast cancer cells. In this study, time- and dose- dependent inhibitory activity were evaluated using MTT assay after 48 h and 72 h exposure time. In addition, median effect analysis was conducted according to Chou-Talalay method to investigate whether MnIII complex has synergistic effect in combination with chemotherapeutic drugs on inhibiting breast cancer cell growth. The molecular mechanisms underlying its potent antiproliferative effect was determined through bioluminescent caspase-3/7, -8 and -9 activity assays and quantitative expression analysis of cell cycle- and apoptosis-related genes. Furthermore, safety evaluation of MnIII complex was assessed through the acute oral toxicity test in in vivo model. The MTT assay results revealed that it potently reduced the viability of MCF-7 (IC50 of 0.63 ± 0.07 µg/mL for 48 h and 0.39 ± 0.08 µg/mL for 72 h) and MDA-MB-231 (1.17 ± 0.06 µg/mL for 48 h, 1.03 ± 0.15 µg/mL for 72 h) cells in dose- and time-dependent manner. Combination treatment also enhanced the cytotoxic effects of doxorubicin but not tamoxifen on inhibiting breast cancer cell growth. The involvement of intrinsic and extrinsic pathway in apoptosis induction was exhibited through the increased activity of caspase-9 and caspase-8, respectively, leading to enhanced downstream executioner caspase-3/7 activity in treated MCF-7 and MDA-MB-231 cells. In addition, gene expression analysis revealed that MnIII complex exerts its antiproliferative effect via up-and down-regulation of p21 and cyclin D1, respectively, along with increased expression of Bax/Bcl-2 ratio, TNF-α, initiator caspase-8 and -10 and effector caspase-3 in MCF-7 and MDA-MB-231 cells. However, the results did not show increased caspase-8 activity in treated MCF-7 cells. Furthermore, in vivo acute oral toxicity test revealed no signs of toxicity and mortality in treated animal models compared to the control group. Collectively, the promising inhibitory effect and molecular and mechanistic evidence of antiproliferative activity of MnIII complex and its safety characterization have demonstrated that it may have therapeutic value in breast cancer treatment worthy of further investigation and development.

Corrigendum to "A Comparison of Wound Healing Rate Following Treatment with Aftamed and Chlorine Dioxide Gels in Streptozotocin-Induced Diabetic Rats".

[This corrects the article DOI: 10.1155/2012/468764.].

Hepatoprotectivity of Panduratin A against liver damage: In vivo demonstration with a rat model of cirrhosis induced by thioacetamide.

This experiment evaluated Panduratin A (PA), a chalcone isolated from Boesenbergia rotunda rhizomes, for its hepatoprotectivity. Rats were subjected to liver damage induced by intra-peritoneal injection of thioacetamide (TAA). PA was tested first for its acute toxicity and then administered by oral gavage at doses 5, 10, and 50 mg/kg to rats. At the end of the 8th week, livers from all rats were excised and evaluated ex vivo. Measurements included alkaline phosphatase (AP), alanine transaminase (ALT), aspartate transaminase (AST) and gamma-glutamyl transferase (GGT), serum platelet-derived growth factor (PDGF) and transforming growth factor (TGF-ß1), and hepatic metalloproteinase enzyme (MMP-2) and its inhibitor extracellular matrix protein (TIMP-1). Oxidative stress was measured by liver malondialdehyde (MDA) and nitrotyrosine levels, urinary 8-hydroxy 2- deoxyguanosine (8-OH-dG), and hepatic antioxidant enzyme activities. The immunohistochemistry of TGF-ß1 was additionally performed. PA revealed safe dose of 250 mg/kg on experimental rats and positive effect on the liver. The results suggested reduced hepatic stellate cells (HSCs) activity as verified from the attenuation of serum PDGF and TGF-ß1, hepatic MMP-2 and TIMP-1, and oxidative stress. The extensive data altogether conclude that PA treatment could protect the liver from the progression of cirrhosis through a possible mechanism inhibiting HSCs activity.