Amelioration of CCl4-induced oxidative stress and hepatotoxicity by Ganoderma lucidum in long evans rats.

Liver disease is a serious health problem affecting people worldwide at an alarming rate. The present study aimed to investigate the protective effects of Ganoderma lucidum against CCl4-induced liver toxicity in rats. The experimental Long Evans rats were divided into five groups, of which four groups were treated with carbon tetrachloride (CCl4). Among the CCl4 treated groups, one of the groups was treated with silymarin and two of them with ethanolic extract of G. lucidum at 100 and 200 mg/Kg body weight. The oxidative stress parameters and endogenous antioxidant enzyme concentrations were assessed by biochemical tests. Liver enzymes ALT, AST, and ALP were determined spectrophotometrically. Histopathological examinations were carried out to assess hepatic tissue damage and fibrosis. Reverse transcription PCR (RT-PCR) was performed to determine the expression of IL-1ß, IL-6, IL-10, TNF-α, and TGF-ß genes. Gas Chromatography-Mass Spectroscopy (GC-MS) analysis revealed that G. lucidum is rich in several phytochemicals including 6-Octadecanoic acid (55.81%), l-( +)-Ascorbic acid 2,6-dihexadecanoate (18.72%), Cis-11-Eicosenamide (5.76%), and Octadecanoic acid (5.26%). Treatment with the G. lucidum extract reduced the elevated ALT, AST, ALP levels, and cellular oxidative stress markers and increased the endogenous antioxidant levels. Histopathology observations revealed that the inflammation, infiltration of immune cells, and aberration of collagen fibers in the hepatocytes were altered by the G. lucidum treatment. The increased expression of inflammatory cytokines TNF-α, TGF-ß, IL-1 ß, and IL-6 were markedly suppressed by G. lucidum extract treatment. G. lucidum also prevented the suppression of protective IL-10 expression by CCl4. This study strongly suggests that G. lucidum extract possesses significant hepatoprotective activity as evidenced by reduced oxidative stress and inflammation mediated by suppression in inflammatory cytokine expression and increased protective IL-10 cytokine expression.

Supplementation of cumin seed powder prevents oxidative stress, hyperlipidemia and non-alcoholic fatty liver in high fat diet fed rats.

The present investigation was an attempt to evaluate the hypoglycemic, lipid-lowering, antioxidant and hepatoprotective effects of cumin (Cuminum cyminum family: Apiaceae) supplementation in high fat (HF) diet fed rats. Male Wistar rats were divided into four groups, such as control, control+ cumin, HF and HF+ cumin. Oral glucose tolerance test, plasma lipids, oxidative stress parameters, antioxidant enzymes activities, and liver dysfunction marker enzyme activities were evaluated. Additionally, histological staining of liver tissue was performed to evaluate the inflammatory cells infiltration, iron deposition and fibrosis. The current investigation demonstrated that 1% (w/w) supplementation of cumin powder significantly reduced HF diet-induced glucose intolerance, epididymal and mesenteric fat wet weights and lipid parameters like triglycerides, total cholesterol and low-density lipoproteins. Oxidative stress-related biomarkers including thiobarbituric acid reactive substances (TBARS), nitric oxide (NO) and advanced oxidation protein product (APOP) were also reduced by cumin supplementation. Moreover, HF-diet increased the activity of hepatic biomarker enzymes such as alanine transaminase (ALT) and alkaline phosphatase (ALP) activities which were significantly reduced by cumin powder supplementation. On the other hand, cumin powder supplementation was able to restore the reduced glutathione level with parallel augmentation of the antioxidant enzymes activities such as superoxide dismutase (SOD) and catalase in liver of HF diet-fed rats. Additionally, histological assessments confirmed that cumin powder supplementation also normalized the fat droplet deposition and inflammatory cells infiltration in the liver of HF diet-fed rats. This study suggests that cumin powder supplementation ameliorates dyslipidemia, oxidative stress and hepatic damage in HF diet-fed rats.

Therapeutic Potentials of Colocasia affinis Leaf Extract for the Alleviation of Streptozotocin-Induced Diabetes and Diabetic Complications: In vivo and in silico-Based Studies.

INTRODUCTION: Hypoglycemia in diabetes mellitus (DM) correlates with hepatic impairment, nephropathy, lipid abnormalities, and oxidative stress and subsequently complicates the disease pathogenesis. Medicinal plants have been used for the management of diabetes since ancient times. In this study, we explored the potentials of Colocasia affinis (CA), a plant known to possess anti-allergic and anti-inflammatory activities, as a remedy for diabetes and related complications. METHODS: We induced diabetes in rats using a single intraperitoneal dose (65 mg/kg) of streptozotocin (STZ). We next treated the rats with an ethanolic extract of leaves of CA to reveal its antidiabetic and organ-protective potentials. Biomarkers of diabetes, inflammation, and oxidative stress were measured using biochemical and histopathological analysis. We also performed molecular docking for three major phytochemicals (kaempferol, myricetin, and rosmarinic acid) of CA. RESULTS: Oral administration of the CA leaves extract at 250 mg/kg and 500 mg/kg doses decreased blood glucose level significantly (p<0.05) in STZ-induced diabetic rats. The extract also considerably attenuated plasma HbA1c levels and normalized blood lipids, glycogen, alanine aminotransferase (ALT), and aspartate aminotransferase (AST). Additionally, treatment with the extract improved kidney complications by decreasing serum creatinine and blood urea nitrogen (BUN) levels. Furthermore, CA leaves extract normalized nitric oxide (NO) and advance oxidative protein products (AOPP) in diabetic rats. The extract also showed significant improvement of the antioxidant enzymes glutathione dismutase (GSH) and superoxide dismutase (SOD) at a dose of 500 mg/kg. Besides, histological investigation demonstrated attenuation of inflammation of the vital organs, including the liver and the kidney. In silico studies revealed that three major phytochemicals (kaempferol, myricetin, and rosmarinic acid) of the ethanolic extract of leaves of CA can inhibit several molecular targets of diabetes and inflammation. CONCLUSION: Collectively, our results demonstrated the therapeutic potentials of CA for the mitigation of diabetes and diabetic complications.

Functionalized hBN as targeted photothermal chemotherapy for complete eradication of cancer cells.

The development of combined anticancer therapeutic techniques has drawn increased attention for enhanced therapeutic efficacy. In this work, we synthesized Near Infrared (NIR) responsive ICG (I) functionalized hexagonal boron-nitride (hBN) as photothermal therapeutic agent (hBNI) and Doxorubicin (Dox)-conjugated Hyaluronic acid (HA) as tumor targeted chemotherapeutic agent (d-HA-Dox). Using adhesion properties of Dopamine (d), the hBNI has been integrated with d-HA-Dox to make a tumor targeted photothermal chemotherapeutic agent (hBNI/d-HA-Dox). The nanostructure of hBNI/d-HA-Dox has been studied using 1H NMR, FTIR, UV-vis-NIR and AFM images. Our in vitro results have provided evidence that hBNI/d-HA-Dox can efficiently damage targeted cancer cells while healthy cells are less affected suggesting that the targeted hBNI/d-HA-Dox nanoparticles work as a complementary antitumor agent with its synergistic co-therapeutic power.

In Vitro and In Vivo Tumor Targeted Photothermal Cancer Therapy Using Functionalized Graphene Nanoparticles.

Despite the tremendous progress that photothermal therapy (PTT) has recently achieved, it still has a long way to go to gain the effective targeted photothermal ablation of tumor cells. Driven by this need, we describe a new class of targeted photothermal therapeutic agents for cancer cells with pH responsive bioimaging using near-infrared dye (NIR) IR825, conjugated poly(ethylene glycol)-g-poly(dimethylaminoethyl methacrylate) (PEG-g-PDMA, PgP), and hyaluronic acid (HA) anchored reduced graphene oxide (rGO) hybrid nanoparticles. The obtained rGO nanoparticles (PgP/HA-rGO) showed pH-dependent fluorescence emission and excellent near-infrared (NIR) irradiation of cancer cells targeted in vitro to provide cytotoxicity. Using intravenously administered PTT agents, the time-dependent in vivo tumor target accumulation was exactly defined, presenting eminent photothermal conversion at 4 and 8 h post-injection, which was demonstrated from the ex vivo biodistribution of tumors. These tumor environment responsive hybrid nanoparticles generated photothermal heat, which caused dominant suppression of tumor growth. The histopathological studies obtained by H&E staining demonstrated complete healing from malignant tumor. In an area of limited successes in cancer therapy, our translation will pave the road to design stimulus environment responsive targeted PTT agents for the safe eradication of devastating cancer.

Functionalized biocompatible WO3 nanoparticles for triggered and targeted in vitro and in vivo photothermal therapy.

We report on dopamine-conjugated hyaluronic acid (HA-D), a mussel-inspired facile capping material that can modify tungsten oxide (WO3) nanoparticles to be both biocompatible and targetable, allowing precise delivery (WO3-HA) to a tumor site. Near-infrared (NIR) irradiated WO3-HA showed a rapid and substantial rise in photothermal heat to complete in vitro thermolysis of malignant MDAMB and A549 cancer cellsbut was found to be relatively less sensitive to normal MDCK cells. A long-term in vivo investigation of ~10 nm HA thickness on WO3 (WO3-HA) nanoparticles demonstrated efficient photo-thermal conversion with time-dependent tumor target accumulation. This long-termin vivo survival study ofWO3-HA showed promising biocompatibility, with a complete recovery from malignant tumor. Due to the importance of keeping simplicity in the design of therapeutic nanoparticles, we therefore expect that this facile scheme (HA-D) would contribute to the biocompatible development of versatile metallic nanoparticles for photothermal applications.