In Vitro and In Vivo Preventive Effects of Thymoquinone against Breast Cancer: Role of DNMT1.

Breast cancer (BC) is one of the most common cancers in women and is a major cause of female cancer-related deaths. BC is a multifactorial disease caused by the dysregulation of many genes, raising the need to find novel drugs that function by targeting several signaling pathways. The antitumoral drug thymoquinone (TQ), found in black seed oil, has multitargeting properties against several signaling pathways. This study evaluated the inhibitory effects of TQ on the MCF7 and T47D human breast cancer cell lines and its antitumor activity against BC induced by a single oral dose (65 mg/kg) of 7,12-dimethylbenzanthracene (DMBA) in female rats. The therapeutic activity was evaluated in DMBA-treated rats who received oral TQ (50 mg/kg) three times weekly. TQ-treated MCF7 and T47D cells showed concentration-dependent inhibition of cell proliferation and induction of apoptosis. TQ also decreased the expression of DNA methyltransferase 1 (DNMT1) in both cancer cell types. In DMBA-treated animals, TQ inhibited the number of liver and kidney metastases. These effects were associated with a reduction in DNMT1 mRNA expression. These results indicate that TQ has protective effects against breast carcinogens through epigenetic mechanisms involving DNMT1 inhibition.

Co-drug development of gallic acid and metformin targeting the pro-inflammatory cytokines for the treatment of breast cancer.

It is well-documented that pro-inflammatory cytokines and inflammation play a significant role in the expansion of cancer disease. Gallic acid (GA), a natural compound, and metformin (Met), a synthetic drug exhibit potent anticancer potential via the distinct molecular mechanism. However, whether both these compounds can act synergistically to preclude and treat cancer is still unknown. This prompted us to scrutinize, the synergism between GA and Met, and that of a new co-drug synthesizing of GA and Met (GA-Met) and investigated the chemo-protective effect against breast cancer with possible intervention of cytokines. In vivo studies were based on chemical carcinogenesis, challenging breast tissue by dimethylbenz[α]anthracene (DMBA). Tumour incidence, tumour burden, pro-inflammatory cytokines in serum, breast, hepatic tissue, macroscopically and histological analysis of mammary tumours were carried out and estimated. GA, Met and GA-Met co-drug exhibited the inhibition of cell proliferation; higher reduction of cell proliferation was observed by GA-Met. The inhibitory effect of GA-Met was linked to cell cycle arrest at G0/G1 phase, along with induction of apoptosis and accumulation in the sub-G1 phase. GA-Met significantly inhibited the cytokines production along with protection against DMBA-induced hyperplasia. Taken altogether, the current result suggests that GA-Met co-drug endows a safe and protective effect against cancer metastasis and can possibly use for the treatment of human breast cancer.

Nanomedicines: intervention in inflammatory pathways of cancer.

Inflammation is a complex defense process that maintains tissue homeostasis. However, this complex cascade, if lasts long, may contribute to pathogenesis of several diseases. Chronic inflammation has been exhaustively studied in the last few decades, for its contribution in development and progression of cancer. The intrinsic limitations of conventional anti-inflammatory and anti-cancer therapies triggered the development of nanomedicines for more effective and safer therapies. Targeting inflammation and tumor cells by nanoparticles, encapsulated with active therapeutic agents, offers a promising outcome with patient survival. Considerable technological success has been achieved in this field through exploitation of tumor microenvironment, and recognition of molecules overexpressed on endothelial cells or macrophages, through enhanced vascular permeability, or by rendering biomimetic approach to nanoparticles. This review focusses on the inflammatory pathways in progression of a tumor, and advancement in nanotechnologies targeting these pathways. We also aim to identify the gaps that hinder the successful clinical translation of nanotherapeutics with further clinical studies that will allow oncologist to precisely identify the patients who may be benefited from nanotherapy at time when promotion or progression of tumor initiates. It is postulated that the nanomedicines, in near future, will shift the paradigm of cancer treatment and improve patient survival.

Correction: Ashraf et al. Inhibition of Microtubule Affinity Regulating Kinase 4 by Metformin: Exploring the Neuroprotective Potential of Antidiabetic Drug through Spectroscopic and Computational Approaches. Molecules 2022, 27, 4652.

The updated affiliation information can be seen in the affiliation part of this correction [...].

Nanomedicine in treatment of breast cancer - A challenge to conventional therapy.

Amongst the various types of cancer, breast cancer is a highly heterogeneous disease and known as the leading cause of death among women globally. The extensive interdisciplinary investigation in nanotechnology and cancer biomedical research has been evolved over the years for its effective treatment. However, the advent of chemotherapeutic resistance in breast cancer is one of the major confront researchers are facing in achieving successful chemotherapy. Research in the area of cancer nanotechnology over the years have now been revolutionized through the development of smart polymers, lipids, inorganic materials and eventually their surface-engineering with targeting ligands. Moreover, nanotechnology further extended and brings in the notice the new theranostic approach which combining the therapy and imaging simultaneously. Currently, research is being envisaged in the area of novel nano-pharmaceutical design viz. liposome, nanotubes, polymer lipid hybrid system, which focuses to make the chemotherapy curative and long-lasting. In this review, we aimed to discuss the recent advancement of different surface-engineered/targeted nanomedicines that improved the drug efficacy in breast cancer.

Pharmacological role of Vitamin C in stress-induced cardiac dysfunction via alteration in Gut microbiota.

There is emerging evidence exhibiting the strong association of gut microbiota with cardiovascular metabolic functions. Cardiac diseases may alter the richness, diversity, and composition of the gut microbiome. Vitamin C (Vit C) plays an important role in many metabolic activities in cardiovascular diseases. In this study, we induced cardiac remodeling by the forced swim stress model in rats, which resulted in dysbiosis. Adult male Wistar rats were designated into the following groups: (i) normal control (NC), (ii) forced swim induced stress (FSIS) control, (iii) FSIS + Vit C treatment, and (iv) Vit C control. Stool samples were collected for estimation for 90 days, and at the end of the study, the animals were killed and heart tissue was isolated for histochemical analysis. We observed a sharp fall in the operational taxonomic unit in the FSIS control animals as compared to NC animals. Treatment with Vit C exhibited a decrease in Bacteroidetes while raising the abundance of spirochetes. Plasma levels of creatine kinase myocardial band (CKMB) in the treatment group reduced to 175.7 ± 3.41 U/L, from 317.7 ± 34.48 U/L in the diabetic control group. Also, the C-reactive protein level in the disease control group was 18 ± 0.93 mg/dl, which reduced to the normal level of 7.53 ± 0.20 mg/dl on treatment with Vit C administration. Our results suggest that FSIS induced cardiac complication is also associated with changes in gut microbial abundance. Higher doses of Vit C, which strengthens the immunity, have shown some positive outcomes on cardiac complications. The abundance of gut microbiota is also associated with the immune system, which in turn marks the impact of a disease. More the richness and diversity of the gut microbiome, healthier is the composition that can withstand the external threats of disease and other major challenges in the environment. Hence microbiome abundance plays an important role in the therapies or future prospects of disease. Histopathological studies support the serological and microbiome examination and warrant the cardioprotective influence of Vit C in the stress-induced cardiac dysfunction model.

Inhibition of Microtubule Affinity Regulating Kinase 4 by Metformin: Exploring the Neuroprotective Potential of Antidiabetic Drug through Spectroscopic and Computational Approaches.

Microtubule affinity regulating kinase 4 (MARK4) regulates the mechanism of microtubules by its ability to phosphorylate the microtubule-associated proteins (MAP's). MARK4 is known for its major role in tau phosphorylation via phosphorylating Ser262 residue in the KXGS motif, which results in the detachment of tau from microtubule. In lieu of this vital role in tau pathology, a hallmark of Alzheimer's disease (AD), MARK4 is a druggable target to treat AD and other neurodegenerative disorders (NDs). There is growing evidence that NDs and diabetes are connected with many pieces of literature demonstrating a high risk of developing AD in diabetic patients. Metformin (Mtf) has been a drug in use against type 2 diabetes mellitus (T2DM) for a long time; however, recent studies have established its therapeutic effect in neurodegenerative diseases (NDs), namely AD, Parkinson's disease (PD) and amnestic mild cognitive impairment. In this study, we have explored the MARK4 inhibitory potential of Mtf, employing in silico and in vitro approaches. Molecular docking demonstrated that Mtf binds to MARK4 with a significant affinity of -6.9 kcal/mol forming interactions with binding pocket's critical residues. Additionally, molecular dynamics (MD) simulation provided an atomistic insight into the binding of Mtf with MARK4. ATPase assay of MARK4 in the presence of Mtf shows that it inhibits MARK4 with an IC50 = 7.05 µM. The results of the fluorescence binding assay demonstrated significant binding of MARK4 with a binding constant of 0.6 × 106 M-1. The present study provides an additional axis towards the utilization of Mtf as MARK4 inhibitor targeting diabetes with NDs.

Risk of colorectal cancer in inflammatory bowel diseases.

Inflammatory bowel diseases (IBDs) are chronic problems of gastrointestinal tract (GIT) with poorly understood aetiology. Patients with any of the two common entities, Crohn's disease (CD) or ulcerative colitis (UD) have significant increased risk of gastrointestinal and extra-intestinal malignancies. Particularly, the colorectal cancer (CRC) and lymphomas are the most frequently associated cancers with IBD. Although the incidence of CRC has declined in the European countries during last 30 years yet the risk among IBD patients remains higher than the healthy people. In the present study, we have described many common factors influencing the onset and advancement of IBD and CRC including the alterations in gut microbiota, changes in the interleukin pathways and tumour necrosis factor. The other common factors are patient age, race, genetics, family history, diet composition, obesity and level of vitamins and minerals in the body. These multiple factors contribute to the higher incidence of CRC among IBD patients.

LC-MS/MS-based metabolic profiling of Escherichia coli under heterologous gene expression stress.

Escherichia coli is frequently exploited for genetic manipulations and heterologous gene expression studies. We have evaluated the metabolic profile of E. coli strain BL21 (DE3) RIL CodonPlus after genetic modifications and subjecting to the production of recombinant protein. Three genetically variable E. coli cell types were studied, normal cells (susceptible to antibiotics) cultured in simple LB medium, cells harboring ampicillin-resistant plasmid pET21a (+), grown under antibiotic stress, and cells having recombinant plasmid pET21a (+) ligated with bacterial lactate dehydrogenase gene grown under ampicillin and standard isopropyl thiogalactoside (IPTG)-induced gene expression conditions. A total of 592 metabolites were identified through liquid chromatography-mass spectrometry/mass spectrometry analysis, feature and peak detection using XCMS and CAMERA followed by precursor identification by METLIN-based procedures. Overall, 107 metabolites were found differentially regulated among genetically modified cells. Quantitative analysis has shown a significant modulation in DHNA-CoA, p-aminobenzoic acid, and citrulline levels, indicating an alteration in vitamin K, folic acid biosynthesis, and urea cycle of E. coli cells during heterologous gene expression. Modulations in energy metabolites including NADH, AMP, ADP, ATP, carbohydrate, terpenoids, fatty acid metabolites, diadenosine tetraphosphate (Ap4A), and l-carnitine advocate major metabolic rearrangements. Our study provides a broader insight into the metabolic adaptations of bacterial cells during gene manipulation experiments that can be prolonged to improve the yield of heterologous gene products and concomitant production of valuable biomolecules.

Genotoxic potential of a novel PDE-4B inhibitor Apremilast by chromosomal aberration and micronucleus assay in mice.

OBJECTIVE: Researchers have confirmed that chronic administration of drugs at high doses causes genotoxicity which serve as first step in development of cancers. Apremilast, a phosphodiesterase-4 inhibitor is Food and Drug Administration (FDA) approved drug for Psoriatic Arthritis. The present study designed to conduct genotoxicity testing using the genotoxic study which give simple, sensitive, economical and fast tools for the assessment of damage of genetic material. METHODS: To conduct genotoxicity study of Apremilast, 60 Swiss albino male mice divided into 6 groups (n = 10). Group1 served as a normal control group without any treatment, Group 2 treated as a disease control and administered with cyclophosphamide 40 mg/kg, IP. Group 3, 4, 5 and 6 treated as test groups and received 10, 20, 40 and 80 mg/kg/day Apremilast respectively. The total duration of study was 13 weeks. At termination day animals were sacrificed and chromosomal aberration assay (BMCAA) and micronucleus assay (BMMNA) were performed to know the genotoxicity potential of Apremilast. RESULTS: The results indicates significant rise in chromosomal aberrations (CA) frequency in bone marrow cells and decrease in the MI of the disease control animals as well as Apremilast treated groups. Further significant (p < 0.001; p < 0.0001) increase in score of micronucleated polychromatic erythrocytes (MNPCEs) and percentage of micronucleated PCEs per 1000 PCEs and decrease in the ratio of polychromatic/normochromatic erythrocytes (PCE/NCE) was observed in micronucleus assay. Genotoxic effect increases with the increase of Apremilast dose. Conclusion: Finding of present indicates that Apremilast shows genotoxic potential on high administration although further detailed toxicity studies required for confirmations.

Antineoplastic influence of nimesulide in chemically induced hepatocellular carcinoma by inhibition of DNA synthesis.

Hepatocellular carcinoma is emerging as one of the most common forms of cancer resulting in thousands of death worldwide. The purpose of this study was to screen nimesulide for anticancer activity in chemically induced hepatocellular carcinoma in Wistar rats as well as in BEL 7402 and HEP G2 cell lines. HCC in rats was induced by administering a single dose of diethyl nitrosamine (150 mg/kg) intraperitoneally. Duration of the in vivo study was 12 weeks and the anticancer potential was further confirmed by in vitro cell line study. Administration of DENA in Wistar rats significantly elevated the levels of serum biochemical parameters and α-feto protein. Treatment with different dose of nimesulide significantly decreased the markedly raised serum levels of biochemical parameters as well as maintained the histology of the liver tissues nearly similar to the normal. Further study of hepatocytes enzymes showed that treatment with nimesulide also improved the antioxidant enzyme levels. Our study also examined the cytotoxicity and DNA synthesis inhibition by nimesulide in BEL 7402 and Hep G2 cell lines. Cell viability was assessed by [3H]-thymidine uptake procedure. The results obtained by in vitro cell line study, histopathological and biochemical data concluded that nimesulide, a preferential COX-2 inhibitor, has anticancer activity, which is by first reducing the formation of reactive oxygen species and second by inhibiting the PGE2 effect via Wnt signaling pathway (cell invasion, angiogenesis, and cell proliferation).

Identification of variants in the mitochondrial lysine-tRNA (MT-TK) gene in myoclonic epilepsy-pathogenicity evaluation and structural characterization by in silico approach.

Variations in mitochondrial genes have an established link with myoclonic epilepsy. In the present study we evaluated the nucleotide sequence of MT-TK gene of 52 individuals from 12 unrelated families and reported three variations in 2 of the 13 epileptic patients. The DNA sequences coding for MT-TK gene were sequenced and mutations were detected in all participants. The mutations were further analyzed by the in silico analysis and their structural and pathogenic effects were determined. All the investigated patients had symptoms of myoclonus, 61.5% were positive for ataxia, 23.07% were suffering from hearing loss, 15.38% were having mild to severe dementia, 69.23% were males, and 61.53% had cousin marriage in their family history. DNA extracted from saliva was used for the PCR amplification of a 440 bp DNA fragment encompassing complete MT-TK gene. The nucleotide sequence analysis revealed three mutations, m.8306T>C, m.8313G>C, and m.8362T>G that are divergent from available reports. The identified mutations designate the heteroplasmic condition. Furthermore, pathogenicity of the identified variants was predicted by in silico tools viz., PON-mt-tRNA and MitoTIP. Secondary structure of altered MT-TK was predicted by RNAStructure web server. Studies by MitoTIP and PON-mt-tRNA tools have provided strong evidences of pathogenic effects of these mutations. Single nucleotide variations resulted in disruptive secondary structure of mutant MT-TK models, as predicted by RNAStructure. In vivo confirmation of structural and pathogenic effects of identified mutations in the animal models can be prolonged on the basis of these findings.

Alteration of serum immunoglobins, C-reactive protein, vitamin D, and electrolyte by atenolol and amlodipine in stress-induced hypertensive rats.

The present study is designed for the assessment of various pathological changes like immunoglobins, C-reactive protein, vitamin D, sodium, potassium, calcium in stress-induced hypertensive rats. Albino Wistar rats of sex male were grouped into six. Each group consists of six animals. Groups were Group I (normal control), Group II (disease control), Group III (amlodipine control), Group IV (atenolol control), Group V (amlodipine treatment), and Group VI (atenolol treatment). Group II, V, and VI animals exposed to regular stress by placing them in cages individually and giving foot electric shocks (1 mA, 50 ms duration with 0.5-1 min of intervals regulated randomly by a computer) along with forced swimming (30 min) in order to induce hypertension in rats. This stress was given two times daily (morning and evening) for regular 15 days. Induction of hypertension was confirmed by measuring the tail arterial pressure of blood and angiotensin II. For next 1 month, Group III and V animals are treated with amlodipine with 1 mg/kg, s.c. dose while Group IV and VI animals were given 10 mg/kg, s.c. the dose of atenolol once daily. At the end of the experimental work, blood collected, rats sacrificed, and serum separated. Serum sodium, potassium, immunoglobins, C-reactive protein, vitamin D, and calcium were measured by semi-auto-analyzer. Stress-induced hypertension in rats produced altered serum sodium, potassium, immunoglobins, C-reactive protein, vitamin D, and calcium level which is restored by atenolol. Administration of amlodipine in animals without hypertension shows alteration in the level of immunoglobins, calcium, vitamin D, and electrolytes.

Triterpenoids principle of Wedelia calendulacea attenuated diethynitrosamine-induced hepatocellular carcinoma via down-regulating oxidative stress, inflammation and pathology via NF-kB pathway.

The aerial part of Wedelia calendulacea have been used in Ayurveda, Unani, Tibetan, Siddha and other folk medicine systems to protect the liver and renal tissue. Liver is considered as primary metabolizing site of body, which is prone to damage by endogenous and exogenous toxicants. A reason for liver toxicity, and major causes of the hepatocellular carcinoma (HCC). 19-α-Hydroxyurs-12(13)-ene-28 oic acid-3-O-ß-D-glucopyranoside (HEG), a triterpenoids found in the higher plants, has been known to possess protective effect against various toxicants. The aim of the current study was to scrutinize the hepatoprotective mechanism of HEG against DEN-induced oxidative stress, hyperproliferation, inflammation and apoptosis tissue injury in Wistar rats. Invitro cell lines study of HEG scrutinized against the Hep-G2 and HuH-7 cells. A single dose of DEN (200 mg/kg) and double dose of phenobarbitol were administered to induce the liver damage in rats; the dose treatment of HEG was terminated at the end of 22 weeks. Macroscopical study was performed for the confirmation of hepatic nodules. The serum and hepatic samples were collected for further biochemical and histopathological analysis. Hepatic; non-hepatic; Phase I and II antioxidant enzymes were also examined. Additionally, we also scrutinized the inflammatory cytokines viz., tumor necrosis factor-α, interlukin-6, interlukin-1ß, and Nuclear factor kappa beta (NF-kB), respectively. Histopathological study was also performed for analyzing the changes during the HCC. HEG confirmed the reduction of growth and deoxyribonucleic acid synthesis of both cell lines. DEN successfully induced the HCC in all group, which was significantly (p < 0.001) altered by the HEG in a dose-dependent manner. The decreased level of pro-inflammatory cytokines and altered membrane-bound enzyme activity were also observed. HEG inhibits the phase I, II and antioxidant enzymes at the effective dose-dependent manner, which were considered as the precursor of the HCC. The alteration of phase I, II and antioxidant enzymes confirmed the inhibition of inflammatory reaction and oxidative stress, which directly or indirectly inhibited the NF-kB expression. Collectively, we can conclude that the HEG inhibited the growth of Hepatocellular carcinoma via attenuating the NF-kB pathway.

Source of CpG Depletion in the HIV-1 Genome.

The dinucleotide CpG is highly underrepresented in the genome of human immunodeficiency virus type 1 (HIV-1). To identify the source of CpG depletion in the HIV-1 genome, we investigated two biological mechanisms: (1) CpG methylation-induced transcriptional silencing and (2) CpG recognition by Toll-like receptors (TLRs). We hypothesized that HIV-1 has been under selective evolutionary pressure by these mechanisms leading to the reduction of CpG in its genome. A CpG depleted genome would enable HIV-1 to avoid methylation-induced transcriptional silencing and/or to avoid recognition by TLRs that identify foreign CpG sequences. We investigated these two hypotheses by determining the sequence context dependency of CpG depletion and comparing it with that of CpG methylation and TLR recognition. We found that in both human and HIV-1 genomes the CpG motifs flanked by T/A were depleted most and those flanked by C/G were depleted least. Similarly, our analyses of human methylome data revealed that the CpG motifs flanked by T/A were methylated most and those flanked by C/G were methylated least. Given that a similar CpG depletion pattern was observed for the human genome within which CpGs are not likely to be recognized by TLRs, we argue that the main source of CpG depletion in HIV-1 is likely host-induced methylation. Analyses of CpG motifs in over 100 viruses revealed that this unique CpG representation pattern is specific to the human and simian immunodeficiency viruses.

Thiamine potentiates chemoprotective effects of ibuprofen in DEN induced hepatic cancer via alteration of oxidative stress and inflammatory mechanism.

Present study, was an effort to scrutinize the molecular and biochemical role of ibuprofen and thiamine combination in diethylnitrosamine (DEN)-induced HCC in Wistar rats. Single intraperitoneal injection of DEN (200 mg/kg) was used for induction of HCC in rats. The rats were divided into eight various groups. DEN induced rats were treated with pure ibuprofen (40 mg/kg) and thiamine in combination for the period of 12th weeks. The protocol was terminated after the 16th week. Exposure of DEN up-regulated the levels of different serum biochemical parameters, antioxidant enzyme level, Alfa-fetoprotein (AFP) and reduced the level of High density lipoprotein (HDL) in Wistar rats along with the alteration in pro-inflammatory cytokines viz., interlukin-6 (IL-6), Tumor necrosis factor (TNF-α) and Interleukin-1ß (IL-1ß) with decrease in body weight. Macroscopic evaluation, revealed DEN group rats confirmed the expansion of hepatic nodules, which were reduced by the individual treatment of ibuprofen and thiamine, but the synergistic treatment of ibuprofen and thiamine confirm the significant reduction of hepatic nodules. Further, this combination possesses the significant chemoprotective effect in DEN-induced HCC by restoring the hepatic enzymes and other biomarkers along with an alteration in pro-inflammatory cytokines. The above result concludes that ibuprofen and thiamine combination possess potent anti-cancerous activity.

Novel glycoside from Wedelia calendulacea inhibits diethyl nitrosamine-induced renal cancer via downregulating the COX-2 and PEG2 through nuclear factor-κB pathway.

A new compound derivative of glycoside 19-α-hydroxy-ursolic acid glucoside (19-α-hydroxyurs-12(13)-ene-28-oic acid-3-O-ß-D-glucopyranoside (HEG) was isolated from whole plant of Wedelia calendulacea (Compositae). The structure was elucidated and established by standard spectroscopy approaches. Diethylnitrosamine (DEN) (200 mg/kg) and ferric nitrilotriacetate (Fe-NTA) (9 mg/kg) were used for induction of renal cell carcinoma (RCC) in the rats. The rats were further divided into different groups and were treated with HEG doses for 22 weeks. Anti-cancer effect in RCC by HEG was dose dependent to restrict the macroscopical changes as compared to DEN + Fe-NTA-control animals. Significant alteration in biochemical parameters and dose-dependent alleviation in Phase I and Phase II antioxidant enzymes were responsible for its chemo-protective nature. HEG in dose-dependent manner was significant to alter the elevated levels of pro-inflammatory cytokines and inflammatory mediators during RCC. The histopathological changes were observed in the HEG pre-treated group, which was proof for its safety concern as far as its toxicity is concerned. The isolated compound HEG can impart momentous chemo-protection against experimental RCC by suppressing the cyclooxygenase (COX-2) and prostaglandin E2 (PGE2) expression via nuclear factor-kappa B (NF-κB) pathway.

Melastoma malabathricum Linn attenuates complete freund's adjuvant-induced chronic inflammation in Wistar rats via inflammation response.

BACKGROUND: Natural products use for arthritis treatment is gaining importance in the medical worldt. Various studies reports medical importance of Melastoma malabathricum Linn. (MM) (Melastomataceae), also known as "putki," has a broad range of health benefits, for its free radical scavenging constituents. The current investigation scrutinizes the antioxidant and anti-inflammatory effect of MM against adjuvant-induced arthritis in experimental rats. METHODS: High-performance thin layer chromatography (HPTLC) was used for estimation of phytochemical-constituents present in the MM extract. Protective effect of MM extract in Wistar rats was estimated using CFA-induced model. The rats were divided into different groups with six rats in each group. All animals received oral administration of MM and indomethacin for 28 days. The body weight and arthritic score were scrutinized at regular intervals. At the end of experimental protocol, the rats were sacrificed, and blood samples were used for antioxidant, hematological parameters, pro-inflammatory and inflammatory mediator, respectively. Histopathological observation was used to evaluate the protective effect of MM extract. RESULT & DISCUSSION: Current study confirmed the preventive effect of MM against adjuvant-induced paw edema, paw redness and arthritic progression. MM significantly (P < 0.001) modulated the oxidative stress parameters as well as hematological parameter induced by CFA. The result also altered the distorted level of proinflammatory mediators and inflammatory mediator, which further reinforce the implication of MM in CFA induced arthritis. Histological analyses of joints of rats showed a reduction in the synovial hyperplasia and mononuclear infiltration in the MM treated group which provides evidence for the antiarthritic effect of MM. CONCLUSION: From above parameters our study states that the MM is capable of restraining the alteration produced via adjuvant-induced arthritis in aminals. The repressing effect of MM could be attributed, at least in part, to antioxidant, hematological and anti-inflammatory effect. Figure Caption: Melastoma Malabathricum Linn Attenuates Complete Freund's Adjuvant-Induced Chronic Inflammation in Wistar rats by Inflammation Response.

Chemomodulatory effect Melastoma Malabathricum Linn against chemically induced renal carcinogenesis rats via attenuation of inflammation, oxidative stress, and early markers of tumor expansion.

Melastoma malabathricum Linn (MM) has high valued for its commercial significance. Indian market (northeast) has great demand for the plants, which extended, its use as a traditional home remedy due to its anti-inflammatory effects. In this study, we scrutinize the therapeutic and protective effect of MM against diethylnitrosamine (DEN) and ferric nitrilotriacetate (Fe-NTA)-induced renal carcinogenesis, renal hyperproliferation, and oxidative stress in rats. Liquid chromatography mass spectroscopy (LC-MS) was used for identification of phytoconstituents. Administration of DEN confirmed the initiation the renal carcinogenesis via enhancing the expansion of tumor incidence. Intraperitoneally, administration of Fe-NTA boost the antioxidant enzymes (phase I), viz., superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), glutathione peroxidase (GPx) and phase II, viz., quinone reductase (QR) and glutathione-S-transferase (GST). It also increased the content of renal lipid peroxidation (LPO), hydrogen peroxidase (H2O2) with decrease content in glutathione content (GSH). It also increased the renal biochemical and non-biochemical parameter. It also confirmed the augment the level of thymidine [3H] incorporation into renal DNA, ornithine decarboxylase (ODC) activity and increased the generation of proinflammatory (TNF-α, IL-6 and IL-ß) and inflammatory mediator (PGE2). We also analyzed the macroscopic and histologic of renal tissue. In addition, the effect of phytoconstituent of MM extract was evaluated in silico and free radical scavenging activity against the DPPH and ABTS free radicals. LC-MS confirmed the presence of quercetin >gallic acid in MM extract. Renal carcinogenesis rats treated with MM (100, 250, and 500 mg/kg) confirmed the significantly (P < 0.001) protective effect via reduction the antioxidant (phase I and phase II) enzymes, biochemical parameter and restore the proinflammatory and inflammatory mediator at dose dependent manner. MM altered the ODC and thymidine activity in renal DNA. The chemoprotective effect of MM was confirmed via decreased the renal tumor incidence, which was confirmed by the macroscopic and histopathological observation. Consequently, our result suggests that MM is a potent chemoprotective agent and suppresses DEN+ Fe-NTA-induced renal carcinogenesis, inflammatory reaction, and oxidative stress injury in Wister rats.

Dual inhibition of arachidonic acid pathway by mulberry leaf extract.

The present work investigates the anti-inflammatory, analgesic and antipyretic activity of methanolic extract of mulberry leaves of variety S-1, S-13 and S-146. The S-146 extract was further evaluated for its efficacy against adjuvant arthritis in albino rats followed by inhibitory potential for COX 1, COX 2 and 5 LOX. The HPLC analysis enumerated the presence of morin, reversterol, scopoletin and 7-hydroxy coumarin as the major constituents. The anti-inflammatory, antipyretic and analgesic activity observed in the present experiment could be accredited to the dual inhibition in the AA pathway. The inhibition of COX and LOX enzymes could be imparted to the presence of resveraterol, morin, scopoletin and 7-hydroxy coumarin.