Apigenin attenuates indomethacin-induced gastric ulcer in rats: emphasis on antioxidant, anti-inflammatory, anti-apoptotic, and TGF-ß1 enhancing activities.

Gastric ulcer disease is associated with significant morbidity and mortality rates. The most two common causes of the ulcer are Helicobacter pylori infection and non-steroidal anti-inflammatory drugs. In the past few decades, a significant decrease in the morbidity and mortality rate has been observed probably due to the discovery of proton pump inhibitors. However, the medications used to treat gastric ulcers impose several nauseous side effects. Therefore, recent studies focus on the use of natural products to treat gastric ulcers. In the current study, gastric ulcer was effectively induced using indomethacin, and the protective effect of apigenin, a potent antioxidant flavonoid, was assessed in comparison to omeprazole. The administration of a single oral indomethacin (50 mg/kg) induced gastric ulcer as manifested by hemorrhagic lesions in the gastric mucosa, increased ulcer index, and histopathological alterations. Indomethacin also increased lipid peroxidation, decreased the activities of the antioxidant enzymes superoxide dismutase (SOD) and catalase, increased the immunoreactivity of the inflammatory markers cyclo-oxygenase-2 (COX-2), tumor necrosis factor-alpha (TNF-α), and nuclear factor-kappa B (NF-κB), increased the transcription of the apoptotic marker, Bax, and decreased that of the antiapoptotic Bcl-2. Indomethacin also decreased the immunoreactivity of transforming growth factor-beta 1 (TGF-ß1). On the other hand, pretreatment with apigenin (10 and 20 mg/kg) resulted in a dose-dependent improvement in the macroscopic and microscopic features of the gastric mucosa in a manner comparable to that of omeprazole. The gastroprotective effects of apigenin may be attributed to its anti-inflammatory, anti-antioxidant, and anti-apoptotic activities as well as enhancing the expression of TGF-ß1. Further experimental and clinical research is required to confirm activity of apigenin as anti-ulcer agent.

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.

Phytochemistry, antioxidant, anticancer, and acute toxicity of traditional medicinal food Biarum bovei (Kardeh).

BACKGROUND: The Biarum species (Kardeh) has been consumed as a traditional functional food and medicine for decades. The current study investigates the phytochemistry, in-vitro and in-vivo bioactivities of methanol extracts of B. bovei. METHODS: The Gas-chromatography mass spectrophotometer (GS/GS-MS) was used to analyze the phytochemical profile of the methanol extracts of B. bovei leaves and corms. The B. bovei extracts (BBE) were also investigated for in-vitro antioxidant, anticancer, and in-vivo acute toxicity (2000 mg/kg) activities. RESULTS: The chemical profiling of BBE revealed mainly fatty acids, phytosterol, alcohols, and hydrocarbon compounds. Namely, Linoleic acid, eliadic acid, palmitic acid, 22,23-dihydro-stigmasterol, and campesterol. The antioxidant activity of BBE ranged between 0.24-3.85 µg TE/mL based on different assays. The extracts also exhibited significant anticancer activity against DU-145 (prostate cancer cells), MCF-7 (human breast adenocarcinoma), and HeLa (human cervical cancer) cell lines with IC50 values ranging between 22.73-44.24 µg/mL. Rats fed on 2000 mg/kg dosage of BBE showed absence of any toxicological sign or serum biochemical changes. CONCLUSION: The detected phytochemicals and bioactivities of BBE scientifically backup the folkloric usage as an important source of nutraceuticals and alternative medicine for oxidative stress-related diseases and carcinogenesis inhibition.

Zinc oxide nanoparticles produced by Zingiber officinale ameliorates acute toxoplasmosis-induced pathological and biochemical alterations and reduced parasite burden in mice model.

BACKGROUND: Although, approximately 30% of the world's population is estimated to be infected with Toxoplasma gondii (T. gondii) with serious manifestations in immunocompromised patients and pregnant females, the available treatment options for toxoplasmosis are limited with serious side effects. Therefore, it is of great importance to identify novel potent, well tolerated candidates for treatment of toxoplasmosis. The present study aimed to evaluate the effect of Zinc oxide nanoparticles (ZnO NPs) synthesized using Zingiber officinale against acute toxoplasmosis in experimentally infected mice. METHODS: The ethanolic extract of ginger was used to prepare ZnO NPs. The produced ZnO NPs were characterized in terms of structure and morphology using Fourier Transformed Infrared Spectroscopy (FTIR), X-Ray Diffraction (XRD), UV- spectroscopy and scanning electron microscopy (SEM). The prepared formula was used in treatment of T. gondii RH virulent strain. Forty animals were divided into four groups, with ten mice per group. The first group was the uninfected, control group. The second group was infected but untreated. The third and the fourth groups received ZnO NPs and Spiramycin orally in a dose of 10 mg/kg and 200 mg/kg/day respectively. The effect of the used formulas on the animals survival rate, parasite burden, liver enzymes -including Alanine transaminase (ALT) and aspartate transaminase (AST)-, nitric oxide (NO) and Catalase antioxidant enzyme (CAT) activity was measured. Moreover, the effect of treatment on histopathological alterations associated with toxoplasmosis was examined. RESULTS: Mice treated with ZnO NPs showed the longest survival time with significant reduction in the parasite load in the livers and peritoneal fluids of the same group. Moreover, ZnO NPs treatment was associated with a significant reduction in the level of liver enzymes (ALT, AST) and NO and a significant increase in the antioxidant activity of CAT enzyme. SEM examination of tachyzoites from the peritoneal fluid showed marked distortion of T. gondii tachyzoites isolated from mice treated with ZnO NPs in comparison to untreated group. T. gondii induced histopathological alterations in the liver and brain were reversed by ZnO NPs treatment with restoration of normal tissue morphology. CONCLUSION: The produced formula showed a good therapeutic potential in treatment of murine toxoplasmosis as demonstrated by prolonged survival rate, reduced parasite burden, improved T. gondii associated liver injury and histopathological alterations. Thus, we assume that the protective effect observed in the current research is attributed to the antioxidant capability of NPs. Based on the results obtained from the current work, we suggest greenly produced ZnO NPs as a chemotherapeutic agent with good therapeutic potential and high levels of safety in the treatment of toxoplasmosis.

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.

Gastro-Protective and Therapeutic Effect of Punica granatum against Stomach Ulcer Caused by Helicobacter Pylori.

Gastric ulcer is a chronic condition that occurs when the mucosa of the stomach is broken. There is a physiological equilibrium between aggressive factors and mucosal defense. The purpose of this research was to compare the prevention level and efficiency of herbal medicinal plants (Punica granatum) to the omeprazole drug. Many groups were prepared from Albino male rats, the first control group (inoculate with H. pylori and fed with standard pellet), the Second group, rats inoculated by H. pylori and prevented with Punica granatum aqueous extracts (PGAE) in two dosages (250mg/kg, 500mg/kg), and last group inoculated by H. pylori and prevented with standard drug omeprazole at the dose (20mg/kg). The results showed that the Ulcer Inhibition % of Punica granatum with a high dose of 500mg/kg and a low dose of 250mg/kg was 84.60±5.48 and 42.87±7.14, respectively. While in the omeprazole treatment group, Ulcer Inhibition % was 24.50±6.35 and this Ulcer Inhibition %  in the Punica granatum treatment groups was significant compared to the omeprazole treatment group and the control group (P=0.0001). PGAE displayed a significant lessening in stomach index and infectious cell proliferation with much cell damage. Although the result of the current study improves, a high dosage of aqueous extracts of plants has more effectiveness than a low dosage of aqueous extracts plants.