The potential of Atorvastatin for chronic lung diseases therapy.

Atorvastatin (ATO) is of the statin class and is used as an orally administered lipid-lowering drug. ATO is a reversible synthetic competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-CoA (HMG-CoA) reductase thus leading to a reduction in cholesterol synthesis. It has recently been demonstrated that ATO has different pharmacological actions, which are unrelated to its lipid-lowering effects and has the ability to treat chronic airway diseases. This paper reviews the potential of ATO as an anti-inflammatory, antioxidant, and anti-proliferative agent after oral or inhaled administration. This paper discusses the advantages and disadvantages of using ATO under conditions associated with those found in the airways. This treatment could potentially be used to support the formulating of ATO as an inhaler for the treatment of chronic respiratory diseases.

Effect of Sulforaphane on cardiac injury induced by sepsis in a mouse model: Role of toll-like receptor 4.

As sepsis is associated with a 50% increase in mortality, sepsis-induced cardiomyopathy has become a critical topic. A multidisciplinary approach is required for the diagnosis and treatment of septic cardiomyopathy. This study looked at Sulforaphane, a natural product that aims to evaluate cardiac function after sepsis, and its likely mechanism of action. Twenty-four adult male Swiss albino mice were randomly divided into 4 equal groups (n=6): sham, CLP, vehicle Sulforaphane (the same amount of DMSO injected IP one hour before the CLP), and Sulforaphane group (one hour before the CLP, a 5mg/kg dose of Sulforaphane was injected). Cardiac tissue levels of toll-like receptor 4 (TLR-4), pro-inflammatory mediators, anti-inflammatory markers, oxidative stress markers, apoptosis markers, and serum cardiac damage biomarkers were assessed using ELISA. Statistical analyses, including t-tests and ANOVA tests, were performed with a significance level of 0.05 for normally distributed data. Compared to the sham group, the sepsis group had significantly elevated levels of TLR-4, IL-6, TNF-α, MIF, F2-isoprostane, caspase-3, cTn-I, and CK-MB (p<0.05). In contrast, the Sulforaphane pre-treated group demonstrated significantly lower levels of these markers (p<0.05). Additionally, Bcl-2 levels were significantly reduced (p<0.05) in the Sulforaphane group. Sulforaphane administration also significantly attenuated cardiac tissue injury (p<0.05). The findings suggest that Sulforaphane can decrease heart damage in male mice during CLP-induced polymicrobial sepsis by suppressing TLR-4/NF-kB downstream signal transduction pathways.

Role of the nuclear receptor subfamily 4a in mast cells in the development of irritable bowel syndrome.

The activation of mast cells (MCs) and mediator release are closely related to the pathophysiology of irritable bowel syndrome (IBS). However, the exact underlying mechanisms are still not completely understood. The nuclear receptor subfamily 4a (Nr4a) is a family of orphan nuclear receptors implicated in regulating MC activation, degranulation, cytokine/chemokine synthesis and release. Acute and chronic stress trigger hypothalamic-pituitaryadrenal axis (HPA) activation to induce the release of corticotropin-releasing hormone (CRH), resulting in MC activation and induction of the Nr4a family. Our newest data showed that Nr4a members were specially over-expressed in colonic MCs of the chronic water-avoidance stress (WAS)-induced visceral hyperalgesia mice, suggesting that Nr4a members might be involved in the pathophysiology of visceral hypersensitivity. In this review, we highlight the present knowledge on roles of Nr4a members in the activation of MCs and the pathophysiology of IBS, and discuss signaling pathways that modulate the activation of Nr4a family members. We propose that a better understanding of Nr4a members and their modulators may facilitate the development of more selective and effective therapies to treat IBS patients.

Regulation of Jun and Fos AP-1 transcription factors by JNK MAPKs signaling cascade in areca nut extract treated KB cells.

The edible endosperm of Areca catechu is recognized as a potent carcinogenic agent either consumed alone or in combination with tobacco. Habitual chewing of areca nut leads to orally potential malignant disorders which are highly effective in malignant transformation and thereby lead to oral carcinogenesis. Human buccal epithelial KB carcinoma cells were used as an experimental cell system to inspect the mechanistic act of aqueous extract of areca nut on biochemical status and their implications on transcriptional activation of cancer signaling cascade that could possibly trigger numerous oncogenic players and finally decides the cells fate. Extract treated cells showed reduced viability with altered balance between oxidants and antioxidants which lead to redox status and which is known to distort various biological processes within the cell system. Results of RT-PCR demonstrated decreased expression of BCl2, cell cycle regulators along with Activator Protein -1 (AP-1) components. While Bax, p16 and p21 mRNAs showed increased expression in extract treated KB cells. Likewise, the translational levels of proliferation cell nuclear antigen (PCNA), tumor suppressor p53, retinoblastoma (Rb) and cyclin dependent kinase 4 (CDK4) were decreased along with AP-1 subunits (c-Jun/c-Fos) with increased protein levels of p21 in extract treated KB cells. Further, the downstream activation and regulation of AP-1 transcription factors could be through stress activated c-Jun - N terminal Kinase (JNK) Mitogen Activated Protein Kinases (MAPKs) which downregulated both Jun and Fos mRNA transcripts in areca nut extract exposed KB cells. Thus, outcome of the study provides insights into mechanistic path of pathogenesis of areca related disorders. Further, it could aid in designing new therapeutic modalities that specific targets these oncogenic players and help in disease management.

Korean Red Ginseng exerts anti-inflammatory and autophagy-promoting activities in aged mice.

BACKGROUND: Korean Red Ginseng (KRG) is a traditional herb that has several beneficial properties including anti-aging, anti-inflammatory, and autophagy regulatory effects. However, the mechanisms of these effects are not well understood. In this report, the underlying mechanisms of anti-inflammatory and autophagy-promoting effects were investigated in aged mice treated with KRG-water extract (WE) over a long period. METHODS: The mechanisms of anti-inflammatory and autophagy-promoting activities of KRG-WE were evaluated in kidney, lung, liver, stomach, and colon of aged mice using semi-quantitative reverse transcription polymerase chain reaction (RT-PCR), quantitative RT-PCR (qRT-PCR), and western blot analysis. RESULTS: KRG-WE significantly suppressed the mRNA expression levels of inflammation-related genes such as interleukin (IL)-1ß, IL-8, tumor necrosis factor (TNF)-α, monocyte chemoattractant protein-1 (MCP-1), and IL-6 in kidney, lung, liver, stomach, and colon of the aged mice. Furthermore, KRG-WE downregulated the expression of transcription factors and their protein levels associated with inflammation in lung and kidney of aged mice. KRG-WE also increased the expression of autophagy-related genes and their protein levels in colon, liver, and stomach. CONCLUSION: The results suggest that KRG can suppress inflammatory responses and recover autophagy activity in aged mice.

Study effect of Baicalein encapsulated/loaded Chitosan-nanoparticle on allergic Asthma pathology in mouse model.

Asthma as chronic airway disease has high prevalence in children and imbalance of Th1/Th2 is a critical mechanism in pathogenesis of the asthma. Baicalein as a cell protective and anti-inflammatory flavonoid may have anti-asthma effect. Therefore, for better using lung, baicalein was used in chitosan-nanoparticle as anti-asthma treatment. Baicalein was loaded and encapsulated in chitosan nanoparticle. The morphology, physical characters (particle size, zeta potential and FT-IR) were analyzed. Drug encapsulation and loading capacity, accumulative release-time were studied. After asthma model producing, the mice were treated with L-B-NP and E-B-NP. At least, MCh challenge test, Cytokines measurement and Lung Histopathology were done. Nanoparticles had average size 285 ± 25 nm with negative charge -2.5 mV. The L-B-NP decreased penh value and E-B-NP decreased inflammation. Both nanoparticles increased IL-12 and decreased IL-5. Also, L-B-NP decreased mucus secretion in bronchi. L-B-NP and E-B-NP control immune-allergo-inflammatory response of asthma. L-B-NP controlled AHR and E-B-NP controlled inflammation that can be used as controlling anti-asthma drug.

Chemokines and chemokine receptors during COVID-19 infection.

Chemokines are crucial inflammatory mediators needed during an immune response to clear pathogens. However, their excessive release is the main cause of hyperinflammation. In the recent COVID-19 outbreak, chemokines may be the direct cause of acute respiratory disease syndrome, a major complication leading to death in about 40% of severe cases. Several clinical investigations revealed that chemokines are directly involved in the different stages of SARS-CoV-2 infection. Here, we review the role of chemokines and their receptors in COVID-19 pathogenesis to better understand the disease immunopathology which may aid in developing possible therapeutic targets for the infection.

Using CRISPR to enhance T cell effector function for therapeutic applications.

T cells are critical to fight pathogenic microbes and combat malignantly transformed cells in the fight against cancer. To exert their effector function, T cells produce effector molecules, such as the pro-inflammatory cytokines IFN-γ, TNF-α and IL-2. Tumors possess many inhibitory mechanisms that dampen T cell effector function, limiting the secretion of cytotoxic molecules. As a result, the control and elimination of tumors is impaired. Through recent advances in genomic editing, T cells can now be successfully modified via CRISPR/Cas9 technology. For instance, engaging (post-)transcriptional mechanisms to enhance T cell cytokine production, the retargeting of T cell antigen specificity or rendering T cells refractive to inhibitory receptor signaling can augment T cell effector function. Therefore, CRISPR/Cas9-mediated genome editing might provide novel strategies for cancer immunotherapy. Recently, the first-in-patient clinical trial was successfully performed with CRISPR/Cas9-modified human T cell therapy. In this review, a brief overview of currently available techniques is provided, and recent advances in T cell genomic engineering for the enhancement of T cell effector function for therapeutic purposes are discussed.

Naringin prevents cyclophosphamide-induced erythrocytotoxicity in rats by abrogating oxidative stress.

Earlier reports have shown that Cyclophosphamide (CYCP), an anti-malignant drug, elicited cytotoxicity; and that naringin has several beneficial potentials against oxidative stress and dyslipidaemias. We investigated the influence of naringin on free radical scavenging, cellular integrity, cellular ATP, antioxidants, oxidative stress, and lipid profiles in the CYCP-induced erythrocytotoxicity rat model. Rats were pretreated orally by gavage for fourteen consecutive days with three doses (50, 100, and 200 mg/kg) naringin before single CYCP (200 mg/kg, i.p.) administration. Afterwards, the rats were sacrificed. Naringin concentrations required for 50 % scavenging hydrogen peroxide and nitric oxide radical were 0.27 mg/mL and 0.28 mg/mL, respectively. Naringin pretreatment significantly (p < 0.05) protected erythrocytes plasma membrane architecture and integrity by abolishing CYCP-induced decrease in the activity of erythrocyte LDH (a marker of ATP). Pretreatment with naringin remarkably (p < 0.05) reversed CYCP-induced decreases in the erythrocytes glutathione levels, activities of glutathione-S-transferase, catalase, glutathione peroxidase, and glutathione reductase; attenuated CYCP-mediated increases in erythrocytes levels of malondialdehyde, nitric oxide, and major lipids (cholesterol, triacylglycerol, phospholipids, and non-esterified fatty acids). Taken together, different acute pretreatment doses of naringin might avert CYCP-mediated erythrocytes dysfunctions via its antioxidant, free-radical scavenging, and anti-dyslipidaemia properties.

Nitric oxide and viral infection: Recent developments in antiviral therapies and platforms.

Nitric oxide (NO) is a gasotransmitter of great significance to developing the innate immune response to many bacterial and viral infections, while also modulating vascular physiology. The generation of NO from the upregulation of endogenous nitric oxide synthases serves as an efficacious method for inhibiting viral replication in host defense and warrants investigation for the development of antiviral therapeutics. With increased incidence of global pandemics concerning several respiratory-based viral infections, it is necessary to develop broad therapeutic platforms for inhibiting viral replication and enabling more efficient host clearance, as well as to fabricate new materials for deterring viral transmission from medical devices. Recent developments in creating stabilized NO donor compounds and their incorporation into macromolecular scaffolds and polymeric substrates has created a new paradigm for developing NO-based therapeutics for long-term NO release in applications for bactericidal and blood-contacting surfaces. Despite this abundance of research, there has been little consideration of NO-releasing scaffolds and substrates for reducing passive transmission of viral infections or for treating several respiratory viral infections. The aim of this review is to highlight the recent advances in developing gaseous NO, NO prodrugs, and NO donor compounds for antiviral therapies; discuss the limitations of NO as an antiviral agent; and outline future prospects for guiding materials design of a next generation of NO-releasing antiviral platforms.

Cytochrome P450 endoplasmic reticulum-associated degradation (ERAD): therapeutic and pathophysiological implications.

The hepatic endoplasmic reticulum (ER)-anchored cytochromes P450 (P450s) are mixed-function oxidases engaged in the biotransformation of physiologically relevant endobiotics as well as of myriad xenobiotics of therapeutic and environmental relevance. P450 ER-content and hence function is regulated by their coordinated hemoprotein syntheses and proteolytic turnover. Such P450 proteolytic turnover occurs through a process known as ER-associated degradation (ERAD) that involves ubiquitin-dependent proteasomal degradation (UPD) and/or autophagic-lysosomal degradation (ALD). Herein, on the basis of available literature reports and our own recent findings of in vitro as well as in vivo experimental studies, we discuss the therapeutic and pathophysiological implications of altered P450 ERAD and its plausible clinical relevance. We specifically (i) describe the P450 ERAD-machinery and how it may be repurposed for the generation of antigenic P450 peptides involved in P450 autoantibody pathogenesis in drug-induced acute hypersensitivity reactions and liver injury, or viral hepatitis; (ii) discuss the relevance of accelerated or disrupted P450-ERAD to the pharmacological and/or toxicological effects of clinically relevant P450 drug substrates; and (iii) detail the pathophysiological consequences of disrupted P450 ERAD, contributing to non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) under certain synergistic cellular conditions.

Solute carrier transporters: the metabolic gatekeepers of immune cells.

Solute carrier (SLC) transporters meditate many essential physiological functions, including nutrient uptake, ion influx/efflux, and waste disposal. In its protective role against tumors and infections, the mammalian immune system coordinates complex signals to support the proliferation, differentiation, and effector function of individual cell subsets. Recent research in this area has yielded surprising findings on the roles of solute carrier transporters, which were discovered to regulate lymphocyte signaling and control their differentiation, function, and fate by modulating diverse metabolic pathways and balanced levels of different metabolites. In this review, we present current information mainly on glucose transporters, amino-acid transporters, and metal ion transporters, which are critically important for mediating immune cell homeostasis in many different pathological conditions.

Melibiosamine, a novel oligosaccharide, suppresses mitogen-induced IL-2 production via inactivation of NFAT and NFκB in Jurkat cells.

d-Glucosamine (GlcNH2) and several of its derivatives are known to possess immunosuppressive activities in various immune cell lines. The novel GlcNH2-containing oligosaccharide Galα1-6GlcNH2 (designated melibiosamine; MelNH2) is expected to be immunosuppressive also. In Jurkat cells (immortalized human T lymphocytes), interleukin 2 (IL-2) production (an index of the T-cell immune response) can be induced by stimulation with a mitogen, such as concanavalin A. Here, we compared the effects of GlcNH2 and MelNH2 on concanavalin A-induced IL-2 production (CIIP) in Jurkat cells and found that GlcNH2 and MelNH2 at millimolar levels both significantly suppressed CIIP without affecting cell viability. When we examined the effects of GlcNH2 and MelNH2 on the activation of the three transcription factors required for CIIP-NFAT (nuclear factor of activated T-cells), NFκB (nuclear factor kappa-light-chain-enhancer of activated B cells), and AP-1 (activator protein 1)-we found that GlcNH2 and MelNH2 both suppressed CIIP by inhibiting the activation of NFAT and NFκB, but, unlike GlcNH2, MelNH2 also promoted the activation of AP-1. These results suggest that MelNH2 may be a potentially useful lead compound for development as an immunosuppressive or anti-inflammatory drug.

4-methoxycinnamyl p-coumarate isolated from Etlingera pavieana rhizomes inhibits inflammatory response via suppression of NF-κB, Akt and AP-1 signaling in LPS-stimulated RAW 264.7 macrophages.

BACKGROUND: 4-methoxycinnamyl p-coumarate (MCC) was isolated from rhizomes of Etlingera pavieana by bioactivity-guided isolation, however, the molecular mechanism underlying its anti-inflammatory activity remains inadequately understood. PURPOSE: In this study, we elucidated the suppressive effect of MCC on LPS-induced expression of inflammatory mediators and the molecular mechanisms responsible for anti-inflammatory activities in RAW 264.7 macrophages. METHODS: Cell viability of MCC-treated RAW 264.7 macrophage was measured by MTT assay. Anti-inflammatory activity was evaluated by measurement of NO, PGE2, and cytokine production in LPS-stimulated cells. qRT-PCR and Western blotting analysis were used to investigate mRNA and protein levels of inflammatory responsive genes. NF-κB activation and transactivation activity were determined by immunofluorescence and reporter gene assay, respectively. RESULTS: MCC considerably suppressed both the production of NO, PGE2, IL-1ß as well as TNF-α and their expression. MCC inactivated NF-κB by reducing phosphorylation of IκBα and inhibiting NF-κB p65 nuclear translocation. Also, MCC significantly inhibited NF-κB transactivation activity. However, the inhibitory effect of MCC was independent of the MAPK signaling pathway. Furthermore, MCC significantly decreased phosphorylation of Akt and c-Jun, a main component of AP-1. CONCLUSION: These findings suggest that the anti-inflammatory effect of MCC could be mediated by the inhibition of LPS-induced expression of inflammatory mediators by down-regulation of the NF-κB, Akt and AP-1 signaling pathways in murine macrophages.

Kinsenoside attenuates osteoarthritis by repolarizing macrophages through inactivating NF-κB/MAPK signaling and protecting chondrocytes.

The objective was to investigate the effect of kinsenoside (Kin) treatments on macrophage polarity and evaluate the resulting protection of chondrocytes to attenuate osteoarthritis (OA) progression. RAW264.7 macrophages were polarized to M1/M2 subtypes then administered with different concentrations of Kin. The polarization transitions were evaluated with quantitative real-time polymerase chain reaction (qRT-PCR), confocal observation and flow cytometry analysis. The mechanism of Kin repolarizing M1 macrophages was evaluated by Western blot. Further, macrophage conditioned medium (CM) and IL-1ß were administered to chondrocytes. Micro-CT scanning and histological observations were conducted in vivo on anterior cruciate ligament transection (ACLT) mice with or without Kin treatment. We found that Kin repolarized M1 macrophages to the M2 phenotype. Mechanistically, Kin inhibited the phosphorylation of IκBα, which further reduced the downstream phosphorylation of P65 in nuclear factor-κB (NF-κB) signaling. Moreover, Kin inhibited mitogen-activated protein kinases (MAPK) signaling molecules p-JNK, p-ERK and p-P38. Additionally, Kin attenuated macrophage CM and IL-1ß-induced chondrocyte damage. In vivo, Kin reduced the infiltration of M1 macrophages, promoted M2 macrophages in the synovium, inhibited subchondral bone destruction and reduced articular cartilage damage induced by ACLT. All the results indicated that Kin is an effective therapeutic candidate for OA treatment.

Molecular and Pathological Events Involved in the Pathogenesis of Diabetes-Associated Nonalcoholic Fatty Liver Disease.

Diabetes mellitus is a rising epidemic in most part of the world and is often associated with multiple organ disorders such as kidney, liver, and cardiovascular diseases. Liver is a major metabolic hub, and the metabolic disorders associated with diabetes result in liver dysfunctions culminating in spectrum of liver diseases such as fatty liver disorders, cirrhosis, and hepatocellular carcinoma. The intervention strategies to prevent diabetes-associated liver injury require an overall understanding of the key factors and molecular pathways which can be strategically targeted. The present review focuses on some of the key aspects of fatty acid metabolism, fetuin-A regulation, inflammatory pathways, and genetic factors associated with insulin resistance, dyslipidemia, hyperglycemia, oxidative stress, and so on involved in the nexus between diabetes and liver injury. Further recent interventions, pharmacological target, and newer therapeutic agents are discussed briefly for the better clinical management of diabetes-associated hepatic disorders.

Application of PD-1 Blockade in Cancer Immunotherapy.

The programmed cell death protein 1 (PD-1) pathway has received considerable attention due to its role in eliciting the immune checkpoint response of T cells, resulting in tumor cells capable of evading immune surveillance and being highly refractory to conventional chemotherapy. Application of anti-PD-1/PD-L1 antibodies as checkpoint inhibitors is rapidly becoming a promising therapeutic approach in treating tumors, and some of them have successfully been commercialized in the past few years. However, not all patients show complete responses and adverse events have been noted, suggesting a better understanding of PD-1 pathway mediated immunosuppression is needed to predict patient response and improve treatment efficacy. Here, we review the progresses on the studies of the mechanistic role of PD-1 pathway in the tumor immune evasion, recent clinical development and commercialization of PD-1 pathway inhibitors, the toxicities associated with PD-1 blockade observed in clinical trials as well as how to improve therapeutic efficacy and safety of cancer immunotherapy.

Targeting receptor tyrosine kinases for chemoprevention by green tea catechin, EGCG.

Tea is one of the most popular beverages consumed worldwide. Epidemiologic studies show an inverse relationship between consumption of tea, especially green tea, and development of cancers. Numerous in vivo and in vitro studies indicate strong chemopreventive effects for green tea and its constituents against cancers of various organs. (-)-Epigallocatechin-3-gallate (EGCG), the major catechin in green tea, appears to be the most biologically active constituent in tea with respect to inhibiting cell proliferation and inducing apoptosis in cancer cells. Recent studies indicate that the receptor tyrosine kinases (RTKs) are one of the critical targets of EGCG to inhibit cancer cell growth. EGCG inhibits the activation of EGFR (erbB1), HER2 (neu/erbB2) and also HER3 (neu/erbB3), which belong to subclass I of the RTK superfamily, in various types of human cancer cells. The activation of IGF-1 and VEGF receptors, the other members of RTK family, is also inhibited by EGCG. In addition, EGCG alters membrane lipid organization and thus inhibits the dimerization and activation of EGFR. Therefore, EGCG inhibits the Ras/MAPK and PI3K/Akt signaling pathways, which are RTK-related cell signaling pathways, as well as the activation of AP-1 and NF-kappaB, thereby modulating the expression of target genes which are associated with induction of apoptosis and cell cycle arrest in cancer cells. These findings are significant because abnormalities in the expression and function of RTKs and their downstream effectors play a critical role in the development of several types of human malignancies. In this paper we review evidence indicating that EGCG exerts anticancer effects, at least in part, through inhibition of activation of the specific RTKs and conclude that targeting RTKs and related signaling pathway by tea catechins might be a promising strategy for the prevention of human cancers.

Effects of endosulfan isomers on cytokine and nitric oxide production by differentially activated RAW 264.7 cells.

Endosulfan is an organochlorine insecticide comprised of two isomers: endosulfan-α and endosulfan-ß. Endosulfan exposure has been shown to elevate some inflammatory factors, such as nitric oxide (NO) and tumor necrosis factor (TNF), in animals or cultures of animal cells. Because the two endosulfan isomers can vary in their biological activities, the goal of this study was to determine if individual endosulfan isomers differentially impact production of NO or TNF by the mouse macrophage cell RAW 264.7 at non-cytotoxic levels. We found elevated TNF with exposure to endosulfan-α (not endosulfan-ß), but only at concentrations that were cytotoxic (≥100 µM), whereas neither endosulfan isomer altered baseline levels of NO at any concentration up to 300 µM. In interferon (IFN)-γ-activated cultures, NO levels were significantly suppressed by either endosulfan isomer at 10 µM (the lowest concentration examined), whereas only endosulfan-ß significantly lowered TNF levels at non-cytotoxic concentrations. In lipopolysaccharide (LPS)-activated cultures, both endosulfan isomers significantly reduced NO, but not TNF, at non-cytotoxic concentrations. These results suggest that the endosulfan isomers have some capacity to alter inflammatory responses differentially, particularly with IFN-γ stimulation.

Anti-inflammatory and preventive activity of white mulberry root bark extract in an experimental model of pancreatitis.

Pancreatitis is characterized by highly morbid inflammation in the pancreas. Currently, there is no specific drug available for pancreatitis except supportive medicines. The present study assessed the pancreato-protective effect of Morus alba root bark extract by using alcohol and cerulein-induced model of pancreatitis. The study also investigated the phytochemical profile through GC-MS and HPLC. Methanolic extract of Morus alba root bark extract (MEMARB) was subjected to GC-MS and HPLC studies. Male albino Wistar rats were administered ethanol (0%-36%) and cerulein (20 µg/kg b.wt. i.p.) with or without MEMARB. Serum lipase, amylase, caspase-1, lipid peroxidation products, glutathione and enzymatic antioxidants were determined. Histological changes in the pancreas were assessed. Cudraflavone B in MEMARB was quantified by HPLC. Significant amount of Cudraflavone B was detected by quantitative HPLC. Marked increase in the levels of serum amylase, lipase, caspase-1, IL-18 and IL-1ß were observed in ethanol and cerulein administered rats than in MEMARB co-administered rats. In MEMARB co-administered rats, the antioxidant status was restored to near normal levels. Histological examinations showed that MEMARB significantly reduced the inflammatory and fibrotic changes. The results reveal the potent pancreato-protective effects of Morus alba root bark. The anti-inflammatory effect of Morus alba root bark extract might be due to the presence of various phytonutrients including Cudraflavone B.