Protective effect of Averrhoa bilimbi L. fruit extract on ulcerative colitis in wistar rats via regulation of inflammatory mediators and cytokines.

Ulcerative Colitis (UC) is a lingering type of Inflammatory Bowel Disease (IBD) which affects the colon mucosa. Ulcerative colitis is majorly associated with oxidative stress and inflammation in colon tissue leading to damage. Averrhoa bilimbi L. fruit is rich in antioxidant phytochemicals including Vitamin C. In the current research, we have evaluated the defence mechanism of Averrhoa bilimbi L. on Ulcerative Colitis (UC). Male wistar rats were treated with Averrhoa bilimbi L. fruit extract (50mg/kg/bwt and 100mg/kg/bwt) and a standard drug Sulfasalazine (100mg/kg/bwt) for 6 consecutive days via intra peritoneally. After one day fasting, rats were given single dose of 3% 2ml of acetic acid through anal (intra-anal) region to induce Ulcerative Colitis. The protective and therapeutic effect of fruit extract on UC was assessed by comparing the relevant changes observed in the normal and treated group. In treated group the level of mucosal injury was decreased (ulcer score - 2) when compared to the control group (ulcer score - 9). The abnormal increase observed in the inflammation mediator cytokines in control rats, i.e IL-1ß, IL-6, TNF-α levels were decreased significantly (**p<0.01) in the Averrhoa bilimbi L. fruit extract treated groups. The increase in weights of the colon tissue and spleen of the control rats were found to be reduced in treated groups. The levels of inflammatory markers iNOS and COX-2 were also decreased in treated group significantly (**p<0.01) when compared with the control. Furthermore, the treatment with Averrhoa bilimbi L. fruit extract has shown a significant antioxidant activity in the UC condition by reducing the levels of NO and enhancing the levels of SOD and GSH in the colon tissue. These results demonstrate the effective anti-ulcerative colitis activity of the Averrhoa bilimbi L. fruit extract in experimental wistar rats.

NF-κB activation and proinflammatory cytokines mediated protective effect of Indigofera caerulea Roxb. on CCl4 induced liver damage in rats.

Indigofera caerulea Roxb. is a well known shrub among native medical practitioners in folk medicine used for the treatment of jaundice, epilepsy, night blindness and snake bites. It is also reported to have antioxidant and antimicrobial properties. However its actual efficacy and hepatoprotective mechanism in particular is uncertain. Thus the present study investigates the hepatoprotective effect of the methanolic extract of I. caerulea Roxb. leaves (MIL) and elucidation of its mode of action against carbon tetrachloride (CCl4) induced liver injury in rats. HPLC analysis of MIL when carried out showed peaks close to standard ferulic acid and quercetin. Intragastric administration of MIL up to 2000 mg/kg bw, didn't show any toxicity and mortality in acute toxicity studies. During "in-vivo" study, hepatic injury was established by intraperitoneal administration of CCl4 3 ml/kg bw (30% CCl4 in olive oil; v/v) twice a week for 4 weeks in Sprague-Dawley rats. Further, hepatoprotective activity of MIL assessed using two different doses (100 and 200mg/kg bw) showed that intra-gastric administration of MIL (200mg/kg bw) significantly attenuates liver injury. Investigation of the underlying mechanism revealed that MIL treatment was capable of reducing inflammation by an antioxidant defense mechanism that blocks the activation of NF-κB as well as inhibits the release of proinflammatory cytokine TNF-α and IL-1ß. The results suggest that MIL has a significant hepatoprotective activity which might be due to the presence of phytochemicals namely analogues of ferulic acid and other phytochemicals which together may suppress the inflammatory signaling pathways and promote hepatoprotective activity against CCl4 intoxicated liver damage.

Modulating effect of Biophytum sensitivum extract on rats with acetic acid-induced ulcerative colitis.

CONTEXT: Traditionally, Biophytum sensitivum (L.) DC (Oxalidaceae) is used in Indian medicine to treat diseases include stomachache, convulsions, cramps, inflammation, and ulcer. OBJECTIVE: The present study examines the effect of aerial parts of B. sensitivum (methanol extract) on a murine model of ulcerative colitis (UC). MATERIALS AND METHODS: UC was induced by intracolonic injection of 3% acetic acid in Wistar rats. B. sensitivum (50 or 100 mg/kg b wt) or reference drug sulfasalazine (100 mg/kg b wt) was administrated intra-peritoneally for 5 consecutive days before induction of colitis. RESULTS: In the present study, we demonstrated for the first time that the administration of B. sensitivum (50 mg/kg b wt) was found to inhibit colitis by lowering macroscopic score (up to 3.66 ± 0.77) and also showed significant reduction (p < 0.01) in lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activities. Furthermore, a significant reduction (p < 0.01) in mucosal content of lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD), and nitric oxide (NO) confirms that B. sensitivum could significantly inhibit colitis. The study showed significant reduction (p < 0.01) in colonic tumor necrosis factor-α (TNF-α), interleukin-1-ß (IL-1ß), and IL-6 levels as well as the expression of inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) after treatment compared with the colitis control group. The histopathological study also confirms the foregoing findings. Treatment with B. sensitivum was also able to inhibit the activation and translocation of transcription factors, nuclear factor (NF)-κB subunits (p65/p50). CONCLUSION: These results suggest that B. sensitivum exhibits protective effect against acetic acid-induced UC.

Amentoflavone inhibits iNOS, COX-2 expression and modulates cytokine profile, NF-κB signal transduction pathways in rats with ulcerative colitis.

Ulcerative colitis is a chronic inflammatory disorder characterized by oxidative stress, leucocyte infiltration and upregulation of pro-inflammatory cytokines. The aim of the present study was to examine the effect of amentoflavone on a murine model of ulcerative colitis (UC). UC was induced by intracolonic injection of 3% acetic acid in male Wistar rats. amentoflavone (10 mg/kg·b.wt) or reference drug sulfasalazine (100 mg/kg·b.wt) was administrated intra-peritoneally for 5 consecutive days before induction of colitis with acetic acid. Administration of amentoflavone was found to reduce the extent of inflammatory colonic injury. This was manifested by a decrease in the score of mucosal injury, by lowered colonic wet weight as well as vascular permeability and diminished lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity reflecting reduced leukocyte infiltration. Furthermore, the mucosal content of lipid peroxidation (LPO), glutathione (GSH), superoxide dismutase (SOD), nitric oxide (NO) activity confirms that amentoflavone could significantly inhibit colitis. The treatment also reduced significantly the colonic tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß) and IL-6 levels as well as the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) compared to colitis control group. The histopathological studies also confirm the foregoing findings. amentoflavone was also able to inhibit the activation and translocation of transcription factors, nuclear factor (NF)-κB subunits (p65/p50). These results suggest that amentoflavone exhibits protective effect in acetic acid-induced ulcerative colitis which might be due to its modulation of oxidant/anti-oxidant balance, down-regulation of productions and expressions of pro-inflammatory cytokines, inflammatory mediators and inhibition of NF-κB signal transduction pathways.

Inhibition of metastatic lung cancer in C57BL/6 mice by marine mangrove Rhizophora apiculata.

Metastasis is one of the hallmarks of malignant neoplasms and is the leading cause of death in many cancer patients. A major challenge in cancer treatment is to find better ways to specifically target tumor metastasis. In this study, the anti-metastatic potential of the methanolic extract of Rhizophora apiculata (R.apiculata) was evaluated using the B16F-10 melanoma induced lung metastasis model in C57BL/6 mice. Metastasis was induced in C57BL/6 mice by injecting highly metastatic B16F-10 melanoma cells through the lateral tail vein. Simultaneous treatment with R.apiculata extract (10 mg/kg b.wt (intraperitoneal) significantly (p<0.01) inhibited pulmonary tumor nodule formation (41.1 %) and also increased the life span (survival rate) 107.3 % of metastatic tumor bearing animals. The administration of R.apiculata extract significantly (p<0.01) reduced biochemical parameters such as lung collagen hydroxyproline, hexosamine, uronic acid content, serum nitric oxide (NO), γ-glutamyl transpeptidase (GGT) and sialic acid levels when compared to metastasis controls. These results correlated with lung histopathology analysis of R.apiculata extract treated mice showing reduction in lung metastasis and tumor masses. Taken together, our findings support that R.apiculata extract could be used as a potential anti-metastasis agent against lung cancer.

Experimental study on anti-tumor and anti-inflammatory effect of Thespesia populnea phytochemical extract in mice models.

In the present study, we have conducted a dose- and duration-dependent response of phytochemical extract of Thespesia populnea (Malvaceae) plant native of costal forest of India. Our earlier studies revealed the anti-oxidant and chemoprotective effect of this plant extract. In the present study, we have attempted to study the anti-tumor and anti-inflammatory response of T. populnea using experimental mouse models. Our studies revealed that administration of T. populnea methanol extract was shown to inhibit the solid tumor development in mice. T. populnea treatment significantly reduced tumor cell glutathione (GSH) levels as well as serum γ-glutamyl transpeptidase (GGT) and nitric oxide (NO) levels in the tumor-bearing animals (p < 0.01). The total white blood cell count and hemoglobin levels were also significantly increased in extract-treated hosts (p < 0.05, p < 0.01). The use of T. populnea substantially reduced the acute inflammation (assessed as paw edema) induced by carrageenan and also reduced inflammation edema induced by formalin. These studies suggest that T. populnea extract could be used as a (natural) anti-inflammatory and anti-tumor agent.

Targeting tumor metastasis by regulating Nm23 gene expression.

The Nm23 gene is a metastatic suppressor identified in a melanoma cell line and expressed in different tumors where their levels of expression are associated with reduced or increased metastatic potential. Nm23 is one of the over 20 metastasis suppressor genes (MSGs) confirmed in vivo. It is highly conserved from yeast to human, implying a critical developmental function. Tumors with alteration of the p53 gene and reduced expression of the Nm23 gene are more prone to metastasis. Nm23-H1 has 3'-5' exonuclease activity. This review focuses on the role of Nm23 in cancer progression and also a potential novel target for cancer therapy.

Tumour lysis syndrome: implications for cancer therapy.

The tumour lysis syndrome (TLS) is a group of metabolic abnormalities caused by rapid and unexpected release of cellular components into the circulation as a result of massive destruction of rapidly proliferating malignant cells. It usually develops in patients with hematologic malignancies like acute lymphoid leukemia, non-Hodgkin and Burkitt's lymphoma after initiation of chemotherapy or may, rarely, occur spontaneously. Though TLS is seldom observed in relation to solid tumours, there have been reports of connections with examples such as lung, liver, breast, gastric carcinomas. The clinical manifestations of TLS include hyperuricemia, hyperkalemia, hyperphosphatemia and hypocalcemia. These indications if untreated lead to life-threatening complications such as acute renal failure, cardiac arrhythmias, seizures, and eventually death due to multiorgan failure. Therefore early detection of TLS is of vital importance. This can be accomplished by identification of high risk patients, implementation of suitable prophylactic measures and monitoring of the electrolyte levels in patients undergoing chemotherapy.

Anticancer activity of Acacia nilotica (L.) Wild. Ex. Delile subsp. indica against Dalton's ascitic lymphoma induced solid and ascitic tumor model.

The aim of the present investigation was to evaluate the effect of A. nilotica extract against Dalton's ascitic lymphoma (DAL) induced solid and ascitic tumors in BALB/c mice. Experimental animals received A. nilotica extract (10 mg/kg.bw) intraperitoneally for 10 and 14 consecutive days before induction of solid and ascitic tumors, respectively. Treatment with A. nilotica extract significantly decreased the development of tumor and percentage increase in body weight when compared to DAL induced solid tumor control group, also increasing the life span, restoring the total white blood cell count and hemoglobin content and significantly decreasing the levels of serum aspartate transaminase (SGPT), alanine transaminase (SGOT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) and nitric oxide (NO) when compared to DAL induced ascitic tumor controls. The treatment also reduced significantly the cellular glutathione (GSH) and nitric oxide levels in treated animals. Histopathological studies also confirmed protective influence. The outcome of the present work indicates that A. nilotica extract could be used as natural anticancer agent for human health.

WAVEs: a novel and promising weapon in the cancer therapy tool box.

The Wiskott-Aldrich Syndrome Protein family Verprolin--homologous proteins (WAVEs), encoded by a metastasis promoter gene, play considerable roles in adhesion of immune cells, cell proliferation, migration and destruction of foreign agents by reactive oxygen species. These diverse functions have lead to the hypothesis that WAVE proteins have multi-functional roles in regulating cancer invasiveness, metastasis, development of tumor vasculature and angiogenesis. Differentials in expression of WAVE proteins are associated with a number of neoplasms include colorectal cancer, hepatocellular cancer, lung squamous cell carcinoma, human breast adenocarcinoma and prostate cancer. In this review we attempt to unify our knowledge regarding WAVE proteins, focusing on their potentials as diagnostic markers and molecular targets for cancer therapy.

Biophytum sensitivum: Ancient medicine, modern targets.

Research on medicinal plants began to focus on discovery of natural products as potential active principles against various diseases. Medicinal plants are very interesting, have the ability to produce remarkable chemical structures with diverse biological activities. Biophytum sensitivum is used as traditional medicine to cure variety of diseases. During the last few decades, extensive research has been carried out to elucidate the chemistry, biological activities, and medicinal applications of B. sensitivum. Phytochemical analysis have shown that the plant parts are rich in various beneficial compounds which include amentoflavone, cupressuflavone, and isoorientin. Extracts and its bioactive compounds have been known to possess antibacterial, anti-inflammatory, antioxidant, antitumor, radioprotective, chemoprotective, antimetastatic, antiangiogenesis, wound-healing, immunomodulation, anti-diabetic, and cardioprotective activity. The present review has been carried out to shed light on the diverse role of this plant in the management of various ailments facing us.

Anti-inflammatory and anti-tumor activity of the marine mangrove Rhizophora apiculata.

A methanolic extract of Rhizophora apiculata was evaluated for its anti-inflammatory and anti-tumor activity against B16F10 melanoma cells in BALB/c mice. The administration of R. apiculata extract was shown to inhibit the solid tumor development in mice. R. apiculata treatment significantly reduced tumor cell glutathione (GSH) levels as well as serum γ-glutamyl transpeptidase (GGT) and nitric oxide (NO) levels in the tumor-bearing animals. The total white blood cell count and hemoglobin levels were also significantly increased in extract-treated hosts. The use of R. apiculata substantially reduced the acute inflammation (assessed as paw edema) induced by carrageenan and also reduced inflammation edema induced by formalin. Analysis of this methanolic extract revealed a high content of 4-pyrrolidinyl, pyrazole, and ketone derivatives. These studies suggest that R. apiculata extract could be used as a (natural) anti-inflammatory and anti-tumor agent.

Chemoprotective effect of Decalepis hamiltonii against cyclophosphamide induced toxicity.

Cancer is a hyper-proliferative disorder that involves transformation, dysregulation of apoptosis, Proliferation, invasion, angiogenesis and metastasis. The conventional methods to treat cancer are surgery, radiotherapy and chemotherapy. Chemotherapy, being a major treatment modality used for the control of advanced stages of malignancies and as a prophylactic against possible metastasis, exhibits severe toxic side effects like diarrhea, fatigue, nausea, vomiting etc. Plants have been used for treating various diseases of human beings since time immemorial. In this study, methanolic extract of Decalepis hamiltonii was studied for its chemoprotective and antioxidant activity. Intraperitoneal administration of the extract significantly increased the total WBC count (3166 +/- 202 cells/cm2), bone marrow cellularity (680 +/- 70.1cells/femur), alpha-esterase positive cells (641 +/- 26.2 cells/4000 cells), Weights of organs such as a spleen and lungs, in Cyclophosphamide (CTX) treated animals when compared to control. D. hamiltonii administration significantly decreased the levels of Serum glutamate pyruvate transaminase (SGPT), Serum glutamate oxaloacetate transaminase (SGOT), creatinine and urea in serum and increased their levels in liver and kidney. Histopathological analysis of small intestine also suggests that extract could reduce the CTX induced intestinal damage. Analysis of the antioxidant status revealed that treatment with D. hamiltonii could significantly inhibit the free radical generation in vitro. Similarly in vivo studies using D. hamiltonii showed that the extract could significantly decrease the level of SOD in serum of the treated animals compared to control animals. In conclusion the finding of this study suggested that the extract from D. hamiltonii has strong chemo protective effect against CTX induced toxicity.

Evaluation of immunostimulant activity and chemoprotective effect of mangrove Rhizophora apiculata against cyclophosphamide induced toxicity in BALB/c mice.

Chemotherapeutic drugs available today are immunosuppressant, cytotoxic and with variety of side effects in cancer chemotherapy. Plant based immunomodulators are often an auxiliary therapy to overcome the repulsive effects of cytotoxic chemotherapeutic agents and to restore immunity with normal health. Mangroves Rhizophora apiculata (R. apiculata) extract was found to protect mice from cyclophosphamide (CTX) induced leukopenia. The leukocyte counts in the R. apiculata extract treated animals was significantly increased (10425 ± 163 mm³) where the control group shows no significant increase (7855 ± 282 mm³). The leukocytes count in CTX induced group treated with R. apiculata extract shows significant increase (5235 ± 303 mm³) when compared with CTX induced group (3416 ± 172 mm³) on the same day. The hemoglobin level of CTX induced group treated with R. apiculata extract shows increase in the level compared with the CTX induced animals. The bone marrow cellularity and α-esterase activity was also significantly higher compared to normal group and CTX induced group. Moreover, R. apiculata extract prevented the loss of organ weight and is increased the organ weight in treated animals. This indicates the efficiency of R. apiculata extract as an effective immunostimulant and better chemoprotectant against CTX induced toxicity in BALB/c mice.

Chemoprotective and immunomodulatory effect of Acacia nilotica during cyclophosphamide induced toxicity.

Most of the synthetic chemotherapeutic agents used today are immunosuppressant and lead to numerous side effects. Plant based immunomodulators are employed as supportive therapy to counteract the undesirable side effects of chemotherapy. In the present study, the immunomodulatory and chemoprotective effect of methanolic extract of Acacia nilotica was investigated in mice. Intraperitoneal administration of the extract was found to significantly increase the Total WBC count, bone marrow cellularity and alpha-esterase positive cells. Cyclophosphamide is a chemotherapeutic drug and induces acute myelosuppression but treatment with the extract was beneficial in ameliorating chemically induced toxicity. The administration of the extract considerably increased the Total WBC count (6800 +/- 733.9 cells/cm2), bone marrow cellularity (43.6 x 10(5) +/- 14.33 cells/femur) and alpha-esterase positive cells (808.6 +/- 8.57 cells/4000 cells) in CTX treated mice when compared to CTX alone treated control mice. Weight of lymphoid organs such as spleen and thymus reduced by CTX were enhanced by treatment with Acacia nilotica extract. It can be concluded that the extract possess immunostimulatory properties.

Myeloperoxidase: the yin and yang in tumour progression.

Myeloperoxidase (MPO) is a heme- containing enzyme abundantly expressed in neutrophils. It catalyzes the reaction between chloride and hydrogen peroxide to generate a potent oxidant, hypochlorous acid (HOCl). It plays an important role in innate immune defense mechanism. However, excessive generation of MPO-derived oxidants has been linked to tissue damage and in the initiation and progression of diseases such as cancer which arise from chronic inflammation. The oxidant activity of MPO is believed to promote the metabolism of chemical carcinogens, cause DNA damage and compromise the repair process. It is also considered as important mediators of gastric ulcers caused by Helicobacter pylori (H. pylori) through its ability to catalyze the generation of reactive oxidants. A G-463 a polymorphism located in the promoter of the MPO gene plays an important role in its transcription. Moreover the reactive oxidants produced by neutrophilic enzyme have the potential to interact with tumour cells and contribute to their metastasis. There has been a considerable interest in the screening of plant extracts and compounds isolated from them for their potential use as HOCl scavengers. This review will discuss the role of MPO in tumour progression and provide an overview of its part in tumour metastasis and ulcer.

Prolyl hydroxylase and hypoxia inducible factor: potential targets for cancer therapy.

Prolyl hydroxylase (PHD) is one of the major enzymes that play a key role in metastasis and angiogenesis. PHD regulates tumor progression by the degradation of hypoxia inducible factor-α (HIF-α), an important factor associated with angiogenesis. This review will provide an overview of the role of PHD and HIF in tumor progression and how it can serve as potential targets for cancer therapy.

All trans retinoic acid and cancer.

All-trans retinoic acid (ATRA) is an active metabolite of vitamin A under the family retinoid. Retinoids, through their cognate nuclear receptors, exert potent effects on cell growth, differentiation and apoptosis, and have significant promise for cancer therapy and chemoprevention. Differentiation therapy with ATRA has marked a major advance and become the first choice drug in the treatment of acute promyelocytic leukemia (APL). Conversions of 13-cis-retinoic acid and 9-cis-retinoic acid to all-trans-retinoic acid is very rapid. Currently, two distinct families of retinoid responsive nuclear receptors have been identified and characterized: retinoic acid receptors (RARs) and retinoid receptors (RXRs), each of which include three isoforms, α,ß,and γ. ATRA is being increasingly included in anti-tumour therapeutical schemes for the treatment of various tumoral diseases such as Kaposi's sarcoma, head and neck squamous cell carcinoma, ovarian carcinoma, bladder cancer, neuroblastoma and has shown antiangiogenic effects in several systems, inhibiting proliferation in vascular smooth muscle cells (VSMCs) and anti-inflammatory in rheumatoid arthritis. This review helps to understand in details about the ATRA and its role on cancer and it is predicted that modulating the activity of ATRA will soon provide novel prevention and treatment approaches for the cancer patients.

Lysyl oxidase: a potential target for cancer therapy.

Lysyl oxidases (LysOX; EC 1.4.3.13, protein-lysine 6-oxidases) are extracellular copper enzymes that catalyze the cross-linking of collagens or elastin in the extracellular matrix (ECM), thereby regulating the tensile strength of tissues. Recent implication of LysOX in cancer, wound healing, cell motility, chemotaxis, and differentiation reflects its remarkable functional diversity and also in the central nervous system pathologies. However, recent reports also demonstrated novel roles for LysOX, including the ability to regulate gene transcription, motility/migration, and cell adhesion. These diverse functions have led researchers to hypothesize that LysOX may have multiple roles affecting both extra- and intracellular cell function(s). Both down and up-regulation of LysOX in tumor tissues and cancer cell lines have been described, suggesting a dual role for LysOX as a tumor suppressor, as well as a metastasis promoter gene. In this review we explain in detail the role of lysyl oxidase in tumor progression and metastasis.

Nitric oxide: pros and cons in tumor progression.

Nitric oxide (NO), synthesized by NO synthase, is a mediator involved in different processes varying from neurotransmission, to affecting the vasculature. The role of NO in tumor development is multifaceted and depends on a variety of conditions that exist with in the cell. This review will discuss the pros and cons of NO in tumor progression and provide an overview of their significant part in metabolism, angiogenesis and their role in the activation of macrophages as well as tumor-associated macrophages. The role of natural products in the regulation of NO will also be discussed.