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Benzene is a notorious toxicant that is responsible for a host of diseases including leukemia. Its concentration in the environment is increasing day-by-day due to excessive automobile use, accelerated industrial activities and cigarette smoke. The awareness on the harmful effects of benzene on health is limited and no antidote has been reported yet. In this study, an attempt has been made to find out a suitable remedy to overcome benzene toxicity in a living organism from a natural source with the seeds of the plant Moringa oleifera (MO). Thirty six Wistar rats were considered for the study and divided into six groups (n=6). While group I remained as control with normal animals, those in groups II - VI received benzene by oral route (800 mg/kg body weight) for 28 consecutive days. On day 29, the benzene-treated animals in groups III - VI received respectively the standard drug ascorbic acid (AA, 25 mg/kg body weight) and MO (50, 100 and 200 mg/kg body weight) for the following 7 days. Group II rats that received only benzene served as negative control without any treatment. On day 36, all the animals were sacrificed and vital organs liver and kidney were removed for studying lipid peroxidation (LPO) and antioxidant markers [Superoxide dismutase (SOD), Total reduced glutathione (TRG), Glutathione peroxidase (GPx) and Catalase (CAT)] in addition to histopathological changes in the tissues. The results of the study revealed that significant changes occurred in the above parameters due to benzene dosing to animals were reverted to near normal values on MO administration in the liver and kidney tissues as compared to untreated animals, suggesting MO's pro-active role in attenuating benzene toxicity. [ABSTRACT FROM AUTHOR]

Lead toxicity and related health issues have become global concern due to increased use of lead-based products in the modern world. Though attempts are being made to tackle this malady through many ways, the use of naturally occurring materials that are available locally is a subtle approach. In this investigation, the fruits of E. officinalis (EO) were studied for their potential in overcoming biochemical and hematological alterations caused by metallic lead in rat model. Four groups of rats, each containing six animals, were considered for the study. Group I served as normal control while to other groups (II-IV), metallic lead powder (100 ppm/rat) was orally administrated for 30 consecutive days. From day 31, the animals in groups III and IV were treated with EO in doses of 50 and 100 mg/kg body weight (p. o.), respectively, for the following seven days. Group II served as lead-treated control. On day 38, the animals in all groups were sacrificed and the blood was collected and serum separated. The changes in biochemical (aspartate aminotrasferase, alanine aminotrasferase, alkaline phosphatase, gamma glutamyltrasferase, total cholesterol, triglycerides, urea, creatinine and calcium) and hematological (red blood cell count, white blood cell count, hemoglobin, packed cell volume and platelet count) parameters were estimated. Lead treated animals in Group - II showed appreciable changes in hematological and biochemical parameters. Treatment with EO (50 and 100 mg/kg) significantly restored the changes in the above parameters to near normal values implying that the fruit of E. officinalis is an effective natural material to overcome widespread lead toxicity. This observation is further supported by histopathological studies of liver and kidney tissues wherein the distorted architecture, degeneration and other changes found in lead-treated animals were brought back to near normal stages by the treatment of EO. [ABSTRACT FROM AUTHOR]

Environmental damage is without a doubt one of the most serious issues confronting society today. As dental professionals, we must recognize that some of the procedures and techniques we have been using may pose environmental risks. The usage and discharge of heavy metals from dental set-ups pollute the environment and pose a serious threat to the ecosystem. Due to the exclusive properties of nanosized particles, nanotechnology is a booming field that is being extensively studied for the remediation of pollutants. Given that the nanoparticles have a high surface area to volume ratio and significantly greater reactivity, they have been greatly considered for environmental remediation. This review aims at identifying the heavy metal sources and their environmental impact in dentistry and provides insights into the usage of nanoparticles in environmental remediation. Although the literature on various functions of inorganic nanoparticles in environmental remediation was reviewed, the research is still confined to laboratory set-ups and there is a need for more studies on the usage of nanoparticles in environmental remediation.

Objective: The objective of the present study was to evaluate the cytotoxic potentials of Evolvulus alsinoides in human hepatoma HepG2 cells. Materials and Methods: HepG2 cells were treated with methanolic extract of E. alsinoides at 20, 40 and 80 µg/ml for 24 hr and cytotoxic effect was analyzed by MTT assay. The apoptosis rate was investigated by Hoechst 33342 and annexin V/propidium iodide staining. Mitochondrial membrane potential was evaluated by rhodamine staining. Also, the expression of catenin – β 1 protein was analyzed by western blotting. Results: E. alsinoides methanolic extract treatment caused significant cytotoxicity in HepG2 cells in a concentration-dependent manner.Dual staining assayconfirmed the presence of early and late apoptotic cells only in extract-treated groups. Plant extract treatment also caused nuclear fragmentation and chromatin condensation in HepG2 cells. Mitochondrial membrane potential also reduced upon E. alsinoides treatments.This treatment also modulated the catenin – β 1 protein expression. Conclusion:In this study, we demonstrated theproapoptotic potential E. alsinoides in HepG2 cells; thus, this plant may be beneficial in the treatment of liver cancer.

Background Drug-induced liver injury is a common cause of acute liver failure. Isoniazid (INH) is used as a first-line treatment for tuberculosis. Clinical and experimental studies have reported abnormal liver function after INH therapy. Lagerstroemia speciosa Pers., commonly known as banaba, has been traditionally used to treat various ailments including diabetes and obesity due to its antioxidant and anti-inflammatory properties. Aim To investigate the hepatoprotective effect of ethanolic banaba leaf extract (EBLE) against INH-induced hepatotoxicity in rats. Materials and methods A total of 30 male Wistar albino rats (150 - 200 g) were divided into five groups (n = 6). Group I rats were served as a control and were administered dimethyl sulfoxide for the first 30 days and water for the next 30 consecutive days. Group II rats were administered INH (50 mg/kg, p.o.) once in the first 30 consecutive days and sacrificed at Day 30. Group III rats were administered INH for 30 consecutive days and left without treatment for the next 30 days. In Groups IV and V, rats were post-treated orally with EBLE 250 and 500 mg/kg, p.o. (0.3 ml/rat) for 30 days after INH administration. At the end of Day 60, the remaining group of animals were sacrificed. The blood and liver tissues were collected. The marker enzymes of hepatotoxicity, oxidative stress markers, inflammatory markers, and histopathology were analyzed. Results INH administration induced significant elevation of marker enzymes (aspartate transaminase, alanine transaminase, alkaline phosphatase, lactate dehydrogenase, bilirubin, gamma-glutamyl transpeptidase) of hepatotoxicity in the serum. This treatment also increased lipid peroxidation and proinflammatory marker expression (tumor necrosis factor-alpha, transforming growth factor-beta, and nuclear factor kappa B (NF-κB) except inhibitor of NF-κB) and decreased antioxidants such superoxide dismutase, catalase, and glutathione in the liver tissue. All these abnormalities were significantly mitigated after treatment with EBLE. Conclusion The results of this study suggest that EBLE can be used for INH-induced hepatotoxicity., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Rohit Singh et al.)

Introduction: Increased colorectal carcinoma (CRC) and osteosarcoma prevalence, low survival rate, poor prognosis, and the limitations of existing anticancer therapies like side effects of drugs, non-specificity, short half-life, etc., pose a need for novel anticancer drugs. Farnesol, an organic sesquiterpene compound, found in the essential oils of various plants has been shown to possess antioxidant, anti-inflammatory, and anticancer properties. However, the anticancer effect of farnesol against CRC and osteosarcoma has not yet been adequately elucidated., Aim: The aim of the study was to analyze the anticancer effects of farnesol against human osteosarcoma and CRC cell lines., Materials and Methods: Human osteosarcoma (Saos-2) and colorectal carcinoma (HCT-116) cell lines were procured and cultured at 37 o C and 5% CO 2 . The cells were treated with 10, 20, 40, 60, 80, and 100 µM/ml and 20, 40, 60, 80, 100, and 120 µM/ml of farnesol for 24 hours, respectively. 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyl tetrazolium bromide assay was performed to assess the cytotoxicity of farnesol on Saos-2 and HCT-116 cells. Acridine orange/ethidium bromide staining was carried out to analyze apoptosis. 4',6-diamidino-2-phenylindole staining was done to observe the nuclear changes. Dichloro-dihydro-fluorescein diacetate staining was performed to assess the farnesol-induced reactive oxygen species (ROS)-mediated cell death., Results: Farnesol reduced the viability and proliferation of Saos-2 and HCT-116 cells in a dose-dependent manner. Farnesol was able to alter the cellular and nuclear morphology of Saos-2 and HCT-116 cells, promoting cell death. Farnesol-induced apoptosis in human osteosarcoma and colorectal carcinoma cell lines. Early apoptosis was observed in farnesol-treated HCT-116 cells. Additionally, ROS-mediated apoptotic cell death was reported in Saos-2 cells., Conclusion: Farnesol has the potential to induce cytotoxicity against human osteosarcoma and CRC cell lines., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Fathima Hinaz et al.)

Introduction Cancer continues to be a significant health issue worldwide, with colorectal cancer (CRC) standing out as one of the most prevalent forms of cancer on a global scale. The lifetime risk of developing CRC is about one in 23 (4.3%) for men and one in 25 (4.0%) for women. Moreover, children and adolescents are frequently reported with osteosarcoma with a low five-year survival rate (69% and 67%, respectively). Aim The aim of the study was to analyze the cytotoxic effects of boldine against human CRC (HCT-116) and osteosarcoma cell lines (Saos-2). Materials and methods HCT-116 and Saos-2 cell lines were subjected to different concentrations of boldine treatment (5, 10, 20, 30, 40, and 50 μg/mL) and (10, 20, 40, 60, and 80 µg/mL), respectively, for 24 hours. The cytotoxicity was analyzed by MTT assay, AO/EB staining, DCFH-DA assay, and scratch assay. Results The MTT assay, microscopic analysis, and staining showed that boldine had dose-dependent cytotoxic effects against HCT-116 and Saos-2 cell lines by inhibiting their proliferation, viability, and migration, and inducing ROS-mediated apoptosis. Conclusion The study concluded that boldine had a concentration-dependent cytotoxic effect on human CRC and osteosarcoma cell lines., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Chandan et al.)

Background Osteosarcoma is the eighth most common cancer and its prevalence in children makes it a global concern. Existing medications and treatments like high-dose methotrexate possess harmful side effects. Therefore, novel herbal drugs like Nelumbo nucifera are of utmost importance. Aim  To analyze a novel anticancer herbal drug, Nelumbo nucifera leaf extract for its cytotoxic potential against osteosarcoma.  Materials and method Nelumbo nucifera leaf extract was prepared. Saos-2 Cells (human osteosarcoma cell line) were treated with Nelumbo nucifera leaf extract (25, 50, 75, 100, 125, and 150 µg/ml) for 24 hours which were then subjected to MTT assay, morphological analysis and DAPI staining. Results The results suggested that Nelumbo nucifera leaf extract had a concentration-dependent cytotoxic effect on Saos-2 cell line. The extract significantly reduced the number of viable cells, inhibited proliferation and induced morphological changes in Saos-2 cells.  Conclusion Nelumbo nucifera has the potential to induce cytotoxicity against osteosarcoma cell lines and hence, this study provides a novel therapeutic regimen for the treatment of osteosarcoma., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Britina et al.)

Nonalcoholic fatty liver disease (NAFLD) is a global health concern associated with significant morbidity and mortality. NAFLD is a spectrum of diseases originating from simple steatosis, progressing through nonalcoholic steatohepatitis (NASH), fibrosis, and cirrhosis that may lead to hepatocellular carcinoma (HCC). The pathogenesis of NAFLD is mediated by the triglyceride accumulation followed by proinflammatory cytokines expression leading to inflammation, oxidative stress, and mitochondrial dysfunction denoted as "two-hit hypothesis", advancing with a "third hit" of insufficient hepatocyte proliferation, leading to the increase in hepatic progenitor cells contributing to fibrosis and HCC. Wnt/β-catenin signaling is responsible for normal liver development, regeneration, hepatic metabolic zonation, ammonia and drug detoxification, hepatobiliary development, etc., maintaining the overall liver homeostasis. The key regulators of canonical Wnt signaling such as LRP6, Wnt1, Wnt3a, β-catenin, GSK-3β, and APC are abnormally regulated in NAFLD. Many experimental studies have shown the aberrated Wnt/β-catenin signaling during the NAFLD progression and NASH to hepatic fibrosis and HCC. Therefore, in this review, we have emphasized the role of Wnt/β-catenin signaling and its modulators that can potentially aid in the inhibition of NAFLD., (Copyright © 2022. Published by Elsevier B.V.)

Thioacetamide (TAA) undergoes bioactivation in the liver by the CYP450 2E1 enzyme, resulting in the formation of TAA-S-oxide and TAA-S-dioxide. TAA-S-dioxide induces oxidative stress via lipid peroxidation of the hepatocellular membrane. A single TAA dose (50-300 mg/kg) administration initiates hepatocellular necrosis around the pericentral region after its covalent binding to macromolecules in the liver. Intermittent TAA administration (150-300 mg/kg, weekly thrice, for 11-16 weeks) activates transforming growth factor (TGF)-β/smad3 downstream signaling in injured hepatocytes, causing hepatic stellate cells (HSCs) to acquire myofibroblast like phenotype. The activated HSCs synthesize a variety of extracellular matrix, leading to liver fibrosis, cirrhosis, and portal hypertension. The TAA induced liver injury varies depending on the animal model, dosage, frequency, and routes of administration. However, TAA induces hepatotoxicity in a reproducible manner, and it is an ideal model to evaluate the antioxidant, cytoprotective, and antifibrotic compounds in experimental animals., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Activated hepatic stellate cells (HSCs)/myofibroblasts are the important sources of cancer-associated fibroblasts in the liver tumor microenvironment (TME). The crosstalk between activated HSCs and tumor cells mediates HCC progression, metastasis, tumor cell survival, angiogenesis and chemoresistance. In TME, HCC cells secrete various soluble factors responsible for the phenotypic activation of quiescent HSCs. Tumor cells use activated HSC-derived extracellular matrix (ECM) for migration and invasion. Further, in liver TME, activated HSCs and sinusoidal endothelial cells engage in a crosstalk that causes the secretion of angiogenesis and metastasis-related growth factors and cytokines. Activated HSCs and immune cells crosstalk to decrease immune surveillance in the liver TME by increasing the population of T regulatory cells and M2 macrophages or myeloid-derived suppressor cells. Thus, HSCs play a vital role in liver TME cell interactions. Therefore, a deep understanding of HSCs activation and their crosstalk with cancer and immune cells in TME may lead to the development of novel therapeutic strategies to target HCC., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Competing Interests: The author declares that he has no conflicts of interest to disclose.

Most anticancer drugs often fail in clinical trials due to poor solubility, poor bioavailability, lack of targeted delivery and several off-target effects. Polymeric nanoparticles such as poly(lactide), poly(lactic- co -glycolic acid), ALB-loading paclitaxel (Abraxane ® ABI-007), lomustine-loaded chitosan, gelatin (decorated with EGF receptor-targeted biotinylated EGF) and so on offer controlled and sustained drug-release properties, biocompatibility and promising anticancer effects. EGF, folic acid, transferrin, sigma and urokinase plasminogen activator receptors-targeting nano preparations improve bioavailability and accumulate drugs on the lung tumor cell surface. However, route of administration, size, pharmacokinetic properties, immune clearance and so on hamper nanomedicines' clinical uses. This review focuses on the benefits, avenues and challenges of nanoparticle-based drug-delivery systems for lung cancer treatment.

Valproic acid (VPA) is an anti-seizure drug that causes idiosyncratic liver injury. 2-propyl-4-pentenoic acid (Δ 4 VPA), a metabolite of VPA, has been implicated in VPA-induced hepatotoxicity. This review summarizes the pathogenesis involved in VPA-induced liver injury. The VPA induce liver injury mainly by i) liberation of Δ 4 VPA metabolites; ii) decrease in glutathione stores and antioxidants, resulting in oxidative stress; iii) inhibition of fatty acid β-oxidation, inducing mitochondrial DNA depletion and hypermethylation; a decrease in proton leak; oxidative phosphorylation impairment and ATP synthesis decrease; iv) induction of fatty liver via inhibition of carnitine palmitoyltransferase I, enhancing nuclear receptor peroxisome proliferator-activated receptor-gamma and acyl-CoA thioesterase 1, and inducing long-chain fatty acid uptake and triglyceride synthesis. VPA administration aggravates liver injury in individuals with metabolic syndromes. Therapeutic drug monitoring, routine serum levels of transaminases, ammonia, and lipid parameters during VPA therapy may thus be beneficial in improving the safety profile or preventing the progression of DILI., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Nonalcoholic fatty liver disease (NAFLD) defines fat accumulation in the liver, and it is commonly associated with metabolic syndromes like diabetes and obesity. Progressive NAFLD leads to nonalcoholic steatohepatitis (NASH) and ultimately causes cirrhosis and hepatocellular carcinoma, and NASH is currently a frequent cause of liver transplantation. Oxidative stress is often contributed to the progression of NAFLD, and hence, antioxidants such as silymarin, silybin, or silibinin, pentoxifylline, resveratrol, and vitamins A, C, and E are used in clinical trials against NAFLD. Silymarin induces the peroxisome proliferator-activated receptor α (PPAR α ), a fatty acid sensor, which promotes the transcription of genes that are required for the enzymes involved in lipid oxidation in hepatocytes. Silybin inhibits sterol regulatory element-binding protein 1 and carbohydrate response element-binding protein to downregulate the expression of genes responsible for de novo lipogenesis by activating AMP-activated protein kinase phosphorylation. Pentoxifylline inhibits TNF- α expression and endoplasmic reticulum stress-mediated inflammatory nuclear factor kappa B (NF- κ B) activation. Thus, it prevents NAFLD to NASH progression. Resveratrol inhibits methylation at Nrf-2 promoters and NF- κ B activity via SIRT1 activation in NAFLD conditions. However, clinically, resveratrol has not shown promising beneficial effects. Vitamin C is beneficial in NAFLD patients. Vitamin E is not effectively regressing hepatic fibrosis. Hence, its combination with antifibrotic agents is used as an adjuvant to produce a synergistic antifibrotic effect. However, to date, none of these antioxidants have been used as a definite therapeutic agent in NAFLD patients. Further, these antioxidants should be studied in NAFLD patients with larger populations and multiple endpoints in the future., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Devaraj Ezhilarasan and Thangavelu Lakshmi.)

Syringic Acid (SA) is a dimethoxybenzene derived from plants. Dietary SA possesses anti-obesity, anti-inflammatory and anti-steatotic effects and is of interest as a potential therapeutic medication in the treatment of obesity, diabetes, diabetic cataracts and asthma. It has anti-tumorigenic effect against hepatocellular carcinoma, lung carcinoma and oral mucosal carcinoma. It is also believed to have a protective effect on Acetaminophen induced damage in Wistar rats. Therefore, it is of interest to document the molecular docking analysis of syringic acid with proteins in inflammatory cascade such as TNF α, NFκB, P50, P65 and IKB for further consideration in drug discovery., Competing Interests: None to declare, (© 2022 Biomedical Informatics.)

Objective: It is of interest to investigate the anti-proliferative effect of β-sitosterol (BS) on human hepatocellular carcinoma (HepG2) cell line., Materials and Methods: β-sitosterol treatments (0.6 and 1.2 mM/ml) were done in HepG2 and after 24 hr, cell viability was evaluated by MTT assay. Reactive oxygen species (ROS) accumulating potential of BS was assessed by dichloro-dihydro-fluorescein diacetate staining. Morphology related to apoptosis was investigated by acridine orange and ethidium bromide dual staining. Cytochrome c and caspase 3 expressions were evaluated by immunofluorescence and western blot analyses., Results: β-sitosterol induced cytotoxicity (p<0.001) and intracellular ROS in HepG2 cells in a dose-dependent manner. BS treatments accumulated induced intracellular ROS accumulation which led to membrane damage and mitochondrial toxicity. At the molecular level, BS treatments induced cytochrome c release from mitochondria and enhanced the protein expressions (p<0.05 vs 0.6 mM/ml and p<0.001 vs 1.2 mM/ml) of both caspase 3 and cleaved caspase 3., Conclusion: β-sitosterol induced ROS accumulation which plays a critical role in apoptosis via the intrinsic pathway in HepG2 cells. The present investigation paves the way for further in vivo studies., Competing Interests: The authors have declared that there is no conflict of interest.

Periodontitis is a most prevalent and infectious multifactorial inflammatory disease and is characterized by the progressive destruction of the tooth-supporting tissues. Porphyromonas gingivalis, a Gram‑negative oral anaerobe, mainly causes periodontitis and it is one of the most important risk factors responsible for aggravation of existing systemic diseases. Several experimental and clinical studies have shown the positive association between periodontitis and different forms of liver disease. Periodontal diseases increase the prevalence of non-alcoholic fatty liver diseases and cirrhosis. Infected periodontium and pathogens in the periodontal microenvironments release pathogen-associated molecular patterns such as peptidoglycan, lipopolysaccharides, gingipain, fimbria, bacterial DNA, etc, and damage-associated molecular patterns such as interleukins-1α, β, - 8, and galectin-3, etc. These virulence factors and cytokines enter the bloodstream, disseminate into the whole body, and induce a variety of systemic pathological effects, including liver diseases (steatosis and fibrosis). Maintaining oral hygiene by scaling and root planning significantly improves liver damage in patients with periodontitis. Dentists and physicians should have more awareness in understanding the bidirectional nature of the relationship between oral and systemic diseases. Importantly, periodontitis condition aggravates simple fatty liver into fibrotic disease and therefore, the aim of this review is to understand the possible link between periodontitis and liver diseases., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Upon liver injury, quiescent hepatic stellate cells (qHSCs), reside in the perisinusoidal space, phenotypically transdifferentiate into myofibroblast-like cells (MFBs). The qHSCs in the normal liver are less fibrogenic, migratory, and also have less proliferative potential. However, activated HSCs (aHSCs) are more fibrogenic and have a high migratory and proliferative MFBs phenotype. HSCs activation is a highly energetic process that needs abundant intracellular energy in the form of adenosine triphosphate (ATP) for the synthesis of extracellular matrix (ECM) in the injured liver to substantiate the injury., Data Sources: The articles were collected through PubMed and EMBASE using search terms "mitochondria and hepatic stellate cells", "mitochondria and HSCs", "mitochondria and hepatic fibrosis", "mitochondria and liver diseases", and "mitochondria and chronic liver disease", and relevant publications published before September 31, 2020 were included in this review., Results: Mitochondria homeostasis is affected during HSCs activation. Mitochondria in aHSCs are highly energetic and are in a high metabolically active state exhibiting increased activity such as glycolysis and respiration. aHSCs have high glycolytic enzymes expression and glycolytic activity induced by Hedgehog (Hh) signaling from injured hepatocytes. Increased glycolysis and aerobic glycolysis (Warburg effect) end-products in aHSCs consequently activate the ECM-related gene expressions. Increased Hh signaling from injured hepatocytes downregulates peroxisome proliferator-activated receptor-γ expression and decreases lipogenesis in aHSCs. Glutaminolysis and tricarboxylic acid cycle liberate ATPs that fuel HSCs to proliferate and produce ECM during their activation., Conclusions: Available studies suggest that mitochondria functions can increase in parallel with HSCs activation. Therefore, mitochondrial modulators should be tested in an elaborate manner to control or prevent the HSCs activation during liver injury to subsequently regress hepatic fibrosis., Competing Interests: Competing interest No benefits in any form have been received or will be received from a commercial party related directly or indirectly to the subject of this article., (Copyright © 2021. Published by Elsevier B.V.)

Background: Silver nanoparticles (AgNP) are commonly used metallic nanoparticles in health care systems. Colon cancer incidence is increasing worldwide. In this study, AgNP was synthesized using β-sitosterol and its cytotoxic potential was evaluated in human colon cancer (HT-29) cells., Methods: Characterization of AgNP was analyzed by TEM and spectrophotometry analysis. HT-29 cells were treated with different concentrations (2, 4, 6, 8 and 10 ng/ml ) of AgNPs and cytotoxicity was evaluated by MTT assay. The apoptosis was analyzed by the flow cytometry. The expression of p53 protein was analyzed by western blotting., Results: β-sitosterol mediated AgNP are spherical in shape and induced concentration-dependent cytotoxicity in HT-29 cells. AgNP caused apoptosis related morphological changes as evidenced by annexin positive staining. AgNP treatments also induced the p53 expression in HT-29 cells., Conclusion: Our present result suggests that β-sitosterol mediated AgNP induce apoptosis in colon cancer cells and this finding may pave the way for further experimental analysis in vivo ., Competing Interests: Conflict of Interest The authors declare they have no conflict of interest., (Copyright© 2021 Avicenna Research Institute.)

Astaxanthin (AXN) is known to have health benefits by epidemiological studies. Therefore, it is of interest to assess the effect of AXN (derived from indigenous unicellular green alga Haematococcus lacustris) to modulate cell cycle arrest, lysosomal acidification and eventually apoptosis using in vitro in A549 lung cancer cells. Natural extracts of astaxanthin were obtained by standardized methods as reported earlier and characterized by standard HPLC and MS. Treatment of A549 cells with AXN (purified fraction) showed significant reduction in cell viability (about 50%) as compared to crude extract at 50µM concentration. Thus, we show the anticancer effects and lysosomal acidification in A549 cells by Astaxanthin from Haematococcus lacustris for further consideration. Together, our results demonstrated the anticancer potential of AXN from Haematococcus lacustris, which is found to be mediated via its ability to induce cell cycle arrest, lysosomal acidification and apoptotic induction., Competing Interests: The authors declare that there are no conflicts of interest., (© 2020 Biomedical Informatics.)

Impact Statement: Portal hypertension is pathologically defined as increase of portal venous pressure, mainly due to chronic liver diseases such as fibrosis and cirrhosis. In fibrotic liver, activated hepatic stellate cells increase their contraction in response to endothelin-1 (ET-1) via autocrine and paracrine stimulation from liver sinusoidal endothelial cells and injured hepatocytes. Clinical studies are limited with ET receptor antagonists in cirrhotic patients with portal hypertension. Hence, studies are needed to find molecules that block ET-1 synthesis. Accumulation of extracellular matrix proteins in the perisinusoidal space, tissue contraction, and alteration in blood flow are prominent during portal hypertension. Therefore, novel matrix modulators should be tested experimentally as well as in clinical studies. Specifically, tumor necrosis factor-α, transforming growth factor-β1, Wnt, Notch, rho-associated protein kinase 1 signaling antagonists, and peroxisome proliferator-activated receptor α and γ, interferon-γ and sirtuin 1 agonists should be tested elaborately against cirrhosis patients with portal hypertension.

Background: Estrogens regulate sexual function and also have a significant role in various pathophysiological processes. Estrogens have a non-reproductive role as the modulators of the immune system, growth, neuronal function, and metabolism. Estrogen receptors are expressed in the liver and their impaired expression and function are implicated with obesity and liver associated metabolic dysfunctions. The purpose of the current review is to discuss the disparity role of estrogens on several forms of liver diseases., Data Sources: A comprehensive search in PubMed and EMBASE was conducted using the keywords "estrogens and liver diseases", "estradiol and liver diseases", "hormones and liver diseases", "endocrine function in liver diseases", and "female hormones in liver diseases". Relevant papers published before September 30, 2019 were included., Results: The present review confirms the imperative role of estrogen in various forms of chronic liver diseases. Estrogens play a key role in maintaining homeostasis and make the liver less susceptible to several forms of chronic liver diseases in healthy premenopausal individuals. In contrast, clinical studies also showed increased estrogen levels with chronic liver diseases., Conclusions: Several studies reported the protective role of estrogens in chronic liver diseases and this has been widely accepted and confirmed in experimental studies using ovariectomized rat models. However, in a few clinical studies, increased estrogen levels are also implicated in chronic liver diseases. Therefore, further studies are warranted at molecular level to explore the role of estrogen in various forms of chronic liver diseases., (Copyright © 2020 First Affiliated Hospital, Zhejiang University School of Medicine in China. Published by Elsevier B.V. All rights reserved.)

Objective: Tamarindus indica Linn. ( T.indica ) is a well-known plant used in traditional medicine. The plant is popular for its antidiabetic activity. However, effect so f its aqueous fruit pulp extract on carbohydrate hydrolyzing enzymes and its glucose uptake potential were not explored., Materials and Methods: The antidiabetic activity was assessed by in-vitro α-amylase and α-glucosidase inhibitory assays after preliminary phytochemical analysis. MTT assay was carried out to find cytotoxicity. Glucose uptake activity of the extract was carried out using L6 myotubes., Results: The results showed a strong α-amylase inhibitory activity for the fruit pulp extract of T.indica compared to standard acarbose; the IC 50 of the fruit pulp extract of T.indica and acarbose was 34.19 µg/ml 34.83µM. The extract also showed moderate α-glucosidase inhibitory activity. IC 50 of the fruit pulp extract of T.indica and acarbose were 56.91µg/ml and 45.69µM respectively. The cytotoxicity assay showed IC 50 of >300µg/ml and ≥1000µM for the fruit pulp extract of T.indica and metformin. The extract showed 63.99±0.08% glucose uptake in L6 myotubes whereas metformin and insulin at 10µg/ml and 10µM exhibited an uptake of 76.99±0.3% and 84.48±0.45% glucose, respectively., Conclusion: The study revealed that the fruit pulp extract of T.indica Linn does not show any cytotoxic effect and has very good α-amylase and good α-glucosidase inhibitory activities. The glucose uptake potential proves its postprandial hypoglycemic effect. Hence, it may be considered an antidiabetic agent for control of postprandial hyperglycemia.

Lichen planus is a chronic inflammatory condition affecting the skin and mucosa. The etiology is unknown but the pathogenesis appears to be an immune-mediated reaction. The mainstay drugs used in the treatment are immunomodulators. The aim of this paper is to report on the therapeutic effectiveness of the alternate medications used in the management of oral lichen planus (OLP). A systematic search of PubMed, Web of Science and Cochrane Controlled Clinical trials were done for all the papers published until December 2019. The search resulted in a total of 20 studies that were found suitable for the review. The results showed that the reduction in pain, treatment effectiveness was comparable between the steroids and alternative medications. However, the alternative medications had a therapeutic advantage in studies that had used placebo as controls and the results were statistically significant ( P < 0.05). No major adverse effects were reported with the usage of alternative medications. There is definitely a therapeutic potential in the usage of alternative medications in the management of OLP. In terms of therapeutic effectiveness, they are on par with the immunomodulators. These alternative medications offer us a new therapeutic option in the management of OLP without any adverse effects., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Oral and Maxillofacial Pathology.)

Background: Syringic acid (SA) has long been used as traditional medicine and is known to have antioxidant, hepatoprotective, neuroprotective and anticancer effects. Studies regarding the anticancer effect of SA against squamous carcinoma cell (SCC)-25, human oral SCC (OSCC) line has not been studied., Aim: This study was aimed to evaluate the cytotoxic potentials of SA in SCC-25 cells., Materials and Methods: Cytotoxic effect of SA was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenylte trazolium bromide assay, using concentrations of 25 and 50 μM/mL for 24 h. At the end of the treatment period, apoptotic markers such as caspase 3 and 9, bcl-2, bax and cytochrome c were evaluated by semiquantitative reverse transcription-polymerase chain reaction. SA-induced morphological changes were investigated by acridine orange/ethidium bromide dual staining., Results: SA inhibited the proliferation and induced cytotoxicity in SCC-25 cells in a concentration-dependent manner. SA treatment caused apoptosis-related morphological changes as evidenced by the dual staining and the modulation of apoptotic marker gene expressions. SA treatments modulated bcl-2/bax homeostasis and increased the expressions of cytochrome c and caspases 3 and 9., Conclusion: SA specifically induces cell death and inhibits the proliferation in OSCC cells through intrinsic/mitochondrial apoptosis pathway, suggesting that SA may be an effective agent for the treatment of human OSCC., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Journal of Oral and Maxillofacial Pathology.)

Objective: The objective of the present study was to evaluate the cytotoxic potentials of Evolvulus alsinoides in human hepatoma HepG2 cells., Materials and Methods: HepG2 cells were treated with methanolic extract of E. alsinoides at 20, 40 and 80 µg/ml for 24 hr and cytotoxic effect was analyzed by MTT assay. The apoptosis rate was investigated by Hoechst 33342 and annexin V/propidium iodide staining. Mitochondrial membrane potential was evaluated by rhodamine staining. Also, the expression of catenin - β 1 protein was analyzed by western blotting., Results: E. alsinoides methanolic extract treatment caused significant cytotoxicity in HepG2 cells in a concentration-dependent manner. Dual staining assay confirmed the presence of early and late apoptotic cells only in extract-treated groups. Plant extract treatment also caused nuclear fragmentation and chromatin condensation in HepG2 cells. Mitochondrial membrane potential also reduced upon E. alsinoides treatments. This treatment also modulated the catenin - β 1 protein expression., Conclusion: In this study, we demonstrated the proapoptotic potential E. alsinoides in HepG2 cells; thus, this plant may be beneficial in the treatment of liver cancer., Competing Interests: None to declare.

Hepatic fibrosis is a pathological lesion, characterized by the progressive accumulation of extracellular matrix (ECM) in the perisinusoidal space and it is a major problem in chronic liver diseases. Phenotypic activation of hepatic stellate cells (HSC) plays a central role in the progression of hepatic fibrosis. Retardation of proliferation and clearance of activated HSCs from the injured liver is an appropriate therapeutic strategy for the resolution and treatment of hepatic fibrosis. Clearance of activated HSCs from the injured liver by autophagy inhibitors, proapoptotic agents and senescence inducers with the high affinity toward the activated HSCs may be the novel therapeutic strategy for the treatment of hepatic fibrosis in the near future., (Copyright © 2018. Published by Elsevier B.V.)

Background: Acacia catechu Willd ( Fabaceae ), commonly known as catechu, cachou, and black cutch, has been studied for its hepatoprotective, antipyretic, antidiarrheal, hypoglycemic, anti-inflammatory, immunomodulatory, antinociceptive, antimicrobial, free radical scavenging, and antioxidant activities., Objective: We evaluated the cytotoxic activity of ethanol extract of A. catechu seed (ACS) against SCC-25 human oral squamous carcinoma cell line., Methods: Cytotoxic effect of ACS extract was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, using concentrations of 0.1-1000 μg/mL for 24 h. A. catechu ethanol seed extract was treated SCC-25 cells with 25 and 50 μg/mL. At the end of treatment period, apoptotic marker gene expressions such as caspase 8, 9, Bcl-2, Bax, and cytochrome c were evaluated by semiquantitative reverse transcription-polymerase chain reaction. Morphological changes of ACS treated SCC-25 cells was evaluated by acridine orange/ethidium bromide (AO/EB) dual staining. Nuclear morphology and DNA fragmentation was evaluated by propidium iodide (PI) staining., Results: A. catechu ethanol seed extract treatment caused cytotoxicity in SCC-25 cells with an IC 50 value of 100 μg/mL. Apoptotic markers caspases 8 and 9, cytochrome c, Bax gene expressions were significantly increased upon ACS extract treatment indicate the apoptosis induction in SCC-25 cells. This treatment also caused significant downregulation of Bcl-2 gene expression. Staining with AO/EB and PI shows membrane blebbing, and nuclear membrane distortion further confirms the apoptosis induction by ACS treatment in SCC-25 cells., Conclusion: The ethanol seed extracts of A. catechu was found to be cytotoxic at lower concentrations and induced apoptosis in human oral squamous carcinoma SCC-25 cells., Summary: Acacia catechu ethanolic seed extract contains phytochemicals such as epicatechin, rutin, and quercetin Acacia catechu seed (ACS) extract significantly ( P < 0.001) inhibits the active proliferation of human oral squamous carcinoma (SCC-25) cellsACS extract treatment to SCC-25 cells significantly modulated the gene expressions pertaining to apoptosis and propidium iodide and acridine orange/ethidium bromide staining also confirm the apoptosis inductionAntiproliferative and apoptosis inducing activities of ACS extract is correlated with phytochemical contents. Abbreviations used: ACS: Acacia catechu seed extract; MTT: 3 (4,5 dimethylthiazol 2 yl) 2,5 diphenyltetrazolium bromide; DMSO: Dimethyl sulfoxide; AO/EO: Acridine orange/ethidium bromide; LC MS: Liquid chromatography mass spectrometry., Competing Interests: There are no conflicts of interest.

Oral cancer is in approximately 30% of all cancers in India. This study was conducted to evaluate the cytotoxic activity of ethanolic extract of Acacia catechu bark (ACB) against human squamous cell carcinoma cell line-25 (SCC-25). Cytotoxic effect of ACB extract was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium Bromide assay. A. catechu extract was treated SCC-25 cells with 25 and 50 μg/mL for 24 h. Apoptosis markers such as caspases-8 and 9, bcl-2, bax, and cytochrome c (Cyt-c) were done by RT-PCR. Morphological changes of ACB treated cells were evaluated using acridine orange/ethidium bromide (AO/EB) dual staining. Nuclear morphology and DNA fragmentation were evaluated using propidium iodide (PI) staining. Further, cell cycle analysis was performed using flow cytometry. A. catechu treatment caused cytotoxicity in SCC-25 cells with an IC 50 of 52.09 μg/mL. Apoptotic marker gene expressions were significantly increased on ACB treatment. Staining with AO/EB and PI shows membrane blebbing and nuclear membrane distortion, respectively, and it confirms the apoptosis induction in SCC-25 cells. These results suggest that ACB extract can be used as a modulating agent in oral squamous cell carcinoma., Competing Interests: There are no conflicts of interest.

Background: Proliferation of hepatic stellate cells (HSCs) plays a pivotal role in the progression of liver fibrosis consequent to chronic liver injury. Silibinin, a flavonoid compound, has been shown to possess anti-fibrogenic effects in animal models of liver fibrosis. This was attributed to an inhibition of cell proliferation of activated HSCs. The present study was to gain insight into the molecular pathways involved in silibinin anti-fibrogenic effect., Methods: The study was conducted on LX-2 human stellate cells treated with three concentrations of silibinin (10, 50 and 100 μmol/L) for 24 and 96 hours. At the end of the treatment cell viability and proliferation were evaluated. Protein expression of p27, p21, p53, Akt and phosphorylated-Akt was evaluated by Western blotting analysis and Ki-67 protein expression was by immunocytochemistry. Sirtuin activity was evaluated by chemiluminescence based assay., Results: Silibinin inhibits LX-2 cell proliferation in dose- and time-dependent manner; we showed that silibinin upregulated the protein expressions of p27 and p53. Such regulation was correlated to an inhibition of both downstream Akt and phosphorylated-Akt protein signaling and Ki-67 protein expression. Sirtuin activity also was correlated to silibinin-inhibited proliferation of LX-2 cells., Conclusion: The anti-proliferative effect of silibinin on LX-2 human stellate cells is via the inhibition of the expressions of various cell cycle targets including p27, Akt and sirtuin signaling.

Background: Proliferation of hepatic stellate cells (HSCs) play pivotal role in the progression of hepatic fibrosis consequent to chronic liver injury. Silibinin (SBN), a flavonoid compound, has shown to possess cell cycle arresting potential against many actively proliferating cancers cell lines. The objective of this study was to evaluate the anti-proliferative and cell cycle arresting properties of SBN in rapidly proliferating human hepatic stellate LX-2 cell line., Methods: LX-2 cells were fed with culture medium supplemented with different concentrations of SBN (10, 50 and 100 μM). After 24 and 96 h of treatment, total cell number was determined by counting. Cytotoxicity was evaluated by trypan blue dye exclusion test. The expression profile of cMyc and peroxisome proliferator-activated receptor-γ (PPAR-γ) protein expressions was evaluated by Western blotting. Oxidative stress marker genes profile was quantified using qPCR. The migratory response of HSCs was observed by scrape wound healing assay., Results: SBN treatments significantly inhibit the LX-2 cell proliferation (without affecting its viability) in dose dependent manner. This treatment also retards the migration of LX-2 cells toward injured area. In Western blotting studies SBN treatment up regulated the protein expressions of PPAR-γ and inhibited cMyc., Conclusion: The present study shows that SBN retards the proliferation, activation and migration of LX-2 cells without inducing cytotoxicity and oxidative stress. The profound effects could be due to cell cycle arresting potential of SBN.

The protective effect of silibinin (SBN) against hepatic fibrosis induced by repeated intermittent administration of N-nitrosodimethylamine (DMN) was investigated in rats. Oral administration of SBN recovered body and liver weight loss and reversed the elevation of serum AST, ALT and ALP accompanied by their fall in the liver tissue in DMN-induced fibrotic rats. Severe oxidative stress induced in fibrotic rats was evidenced by two to three fold elevation in MDA and protein carbonyl levels associated with a fall in the activities of SOD and CAT in repeated DMN treatment and this adversity was protected by SBN post-treatment. Further, the fall in the activities of ATPases and increase in the levels of hydroxyproline and collagen observed in the liver tissue of DMN treated rats was prevented and reversed back toward normalcy by SBN post-treatment. Recovery of rat liver tissue against DMN-induced hepatocellular necrosis, inflammatory changes and hepatic fibrosis by SBN treatment is also confirmed by both H & E and Masson's trichrome stained histopathological evaluation of liver tissue. In conclusion, SBN exhibit hepatoprotective, antioxidant, free radical scavenging, membrane stabilizing and anti-fibrotic activity against DMN-induced hepatic fibrosis suggesting that it may be useful as a therapeutic agent toward amelioration of hepatic fibrosis., (Copyright © 2012 Elsevier B.V. All rights reserved.)