Neuroprotective effect of Mulmina Mango against chemotherapy-induced cognitive decline in mouse model of mammary carcinoma.

The post-treatment status of breast cancer survivors has become a concern because of the toxicity induced by chemotherapeutic agents in the brain tissues resulting in cognitive deficits, which is generally referred as chemobrain. The aim of this study was to assess the effect of a proprietary ayurvedic formulation Mulmina Mango against chemotherapy-induced cognitive impairment (CICI). Mammary carcinoma was induced by subcutaneously inoculating 4T1 cells into the mammary fat pad of the animals. Intraperitoneal administration of Cyclophosphamide, Methotrexate, 5-Fluorouracil (CMF) regimen was carried out once a week for three weeks. Treatment of Mulmina began one week before chemotherapy and continued till the end of the chemotherapy cycle. After three cycles of chemotherapy, cognitive decline was assessed by Morris water maze task followed by assessment of locomotor activity by open-field test. Tumor progression was evaluated by measurement of tumor volume. Oxidative and neuroinflammatory markers were also evaluated from the isolated brain samples. CMF treatment resulted in a considerable reduction in tumour volume. We found chemotherapy negatively affected behavioral and biochemical parameters in animals and Mulmina treatment ameliorated these cognitive impairments by restoring antioxidant and maintaining cytokine levels. The combination of phytochemicals in Mulmina proved its possible ability to alleviate CICI without affecting chemotherapeutic efficiency and could pave the way for identifying treatment strategies to combat chemobrain.

Cognition enhancing effect of rosemary (Rosmarinus officinalis L.) in lab animal studies: a systematic review and meta-analysis.

Patients with mild cognitive impairment eventually progress to Alzheimer's disease (AD) causing a strong impact on public health. Rosmarinus officinalis has long been known as the herb of remembrance and can be a potential cognition enhancer for AD. The aim of this review was to summarize the qualitative and quantitative aspects of R. officinalis and its active constituents in enhancing cognition. A structured search was conducted on Google Scholar and PubMed to find relevant studies that assessed the effect of R. officinalis extract or any of its active constituents on cognitive performance in animals. The following information was extracted from each study: 1) article information; 2) characteristics of study animals; 3) type of intervention: type, dose, duration, and frequency of administration of R. officinalis; and 4) type of outcome measure. Data were analyzed using Review Manager and meta-analysis was performed by computing the standardized mean difference. Twenty-three studies were selected for qualitative analysis and fifteen for meta-analysis. From the fifteen included papers, 22 with 35 comparisons were meta-analyzed. Effect sizes for intact and cognitively impaired animals were 1.19 (0.74, 1.64) and 0.57 (0.19, 0.96), indicating a positive effect on both groups. The subgroup analyses showed substantial unexplained heterogeneity among studies. Overall, R. officinalis improved cognitive outcomes in normal and impaired animals, and results were robust across species, type of extract, treatment duration, and type of memory. However, studies had a considerable amount of heterogeneity, and subgroup analyses failed to find any heterogeneity moderator.

Pinocembrin enriched fraction of Elytranthe parasitica (L.) Danser induces apoptosis in HCT 116 colorectal cancer cells.

BACKGROUND: Colorectal cancer (CRC) is a highly predominant malignancy affecting millions worldwide. Plants belonging to Loranthaceae family have remarkable chemopreventive properties. OBJECTIVE: The goal of the present study was to assess the antiproliferative and apoptosis-inducing effects of stem parts of Elytranthe parasitica (L.) Danser (EP) on colorectal cancer and identify the bioactive phytochemicals. MATERIAL AND METHODS: EP methanol extract (EP.M) and its subsequent fractions were screened for antiproliferative activity in human colorectal carcinoma HCT 116 cell line. Phytocomposition of the bioactive fraction was analyzed by GC-MS. Further, apoptotic induction and cell cycle arrest was assessed in the most bioactive fractions. RESULTS: EP.DEE (Diethyl Ether) fraction and a subsequent fraction derived by column chromatography, Fraction 3A (FR 3A) significantly inhibited the proliferation of HCT 116 cells (P < 0.05). FR 3A triggered apoptosis and notably modulated the cell cycle checkpoints. GC-MS analysis of FR 3A revealed the presence of 24 phytochemicals, the most prominent of which was pinocembrin (70.67%), a flavonoid. CONCLUSION: Hence, it could be speculated that pinocembrin and its related derivatives may be the chief phytochemicals involved in apoptosis - mediated cytotoxicity of the enriched fraction. Our findings indicate the enriched fraction is a promising candidate which could be developed into a natural chemotherapeutic product for colorectal cancer therapy.

Pro-apoptotic and cytotoxic effects of enriched fraction of Elytranthe parasitica (L.) Danser against HepG2 Hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC), the most common type of liver cancer accounts for more than one million deaths worldwide. Current treatment modality for HCC is marginally effective. Plants belonging to Mistletoe family (Loranthaceae) have been used in chemotherapy for many years. The present study was aimed at exploring the anti-proliferative, pro-oxidant and pro-apoptotic potential of stem of Elytranthe parasitica (L.) Danser (EP), a parasitic shrub belonging to Loranthaceae. METHODS: Elytranthe parasitica (L.) Danser, a climbing parasitic shrub was investigated for its cytotoxic activity against HepG2, a hepatocellular carcinoma cell line by Sulforhodamine B (SRB) assay. Further, pro-oxidant activity of EP extract/fractions was studied using copper phenanthroline assay. To understand the mechanism of cell death, the pro-apoptotic effects of Hep-G2 cells treated with EP extract/fractions were visualized by dual staining using acridine orange and ethidium bromide, a morphological marker of apoptosis. Phytochemical profiling of EP was explored by estimating the phenol, flavonoid and tannin content in its various fractions and extract. The occurrence of gallic acid, a principal polyphenol in EP extract and fractions was detected and further quantified using HPTLC (High Performance Thin Layer Chromatography) fingerprinting. RESULT: Active fraction of Elytranthe parasitica, EP.DEE exhibited potent cytotoxic activity in a dose dependent manner against HepG2 hepatocellular carcinoma cell line with an IC50 of 56.7 ± 7.8 µg/mL. Dual staining with acridine orange and ethidium bromide revealed that HepG2 cells treated with EP active fractions underwent cell death chiefly by apoptosis. Highest phenol, flavonoid and tannin content were observed in active fractions, EP.EA (Ethyl acetate fraction) and EP.DEE (Diethyl ether fraction). Gallic acid was identified and quantified in EP extract and active fractions, EP.DEE and EP.EA. CONCLUSION: Our findings indicate EP active fraction could be a promising contender in the treatment of hepatocellular carcinoma.

Oil-material fractionation in Gulf deep water horizontal intrusion layer: Field data analysis with chemodynamic fate model for Macondo 252 oil spill.

Among the discoveries of the Deepwater Horizon blowout was the so-called "sub-surface plume"; herein termed the "oil-trapping layer". Hydrocarbons were found positioned at ~1100-1300m with thickness ~100-150m and moving horizontally to the SW in a vertically stratified layer at the junction of the cold abyssal water and the permanent thermocline. This study focuses on its formation process and fate of the hydrocarbons within. The originality of this work to the field is two-fold, first it provides a conceptual framework which places layer origin in the context of a horizontal "intrusion" from the near-field, vertical, blow-out plume and second, it offers a theoretical model for the hydrocarbon chemicals within the horizontal layer as it moves far-afield. The model quantifies the oil-material fractionation process for the soluble and fine particle. The classical Box model, retrofitted with an internal gradient, the "G-Box", allows an approach that includes turbulent eddy diffusion coupled with droplet rise velocity and reactive decay to produce a simple, explicit, transparent, algebraic model with few parameters for the fate of the individual fractions. Computations show the soluble and smallest liquid droplets moving very slowly vertically through the layer appearing within the trapping layer at low concentration with high persistence. The larger droplets move-through this trapping zone quickly, attain high concentrations, and eventually form the sea surface slick. It impacts the field of oil spill engineering science by providing the conceptual idea and the algorithms for projecting the quantities and fractions of oil-material in a deep water, horizontal marine current being dispersed and moving far afield. In the field of oil spill modeling this work extends the current generation near-field plume source models to the far-field. The theory portrays the layer as an efficient oil-material trap. The model-forecasted concentration profiles for alkanes and aromatics against the available field data support the proposed theory and the resulting model.

Standardised extract of safed musli (Chlorophytum borivilianum) increases aphrodisiac potential besides being safe in male Wistar rats.

The standardised extract of root of safed musli (Chlorophytum borivilianum) was evaluated for its aphrodisiac potential and safety profile on reproductive system. Wistar albino rats were trained to provide sexual experience under a dim red light (10 W) in a glass tank. Male and female rats were placed periodically in the glass tank in a particular order, that is male followed by introduction of the receptive female. Dosing of extract was carried out for 54 days at 125 and 250 mg kg-1 p.o to male rats. On 14th and 28th days, the animals were observed from the cage side for sexual behaviours. Safed musli at both dose levels enhanced sexual vigour and libido which might be useful for treatment of sexual dysfunction in male till 28th day. Safety profile was assessed after 54 days of drug treatment, where both doses showed an increase in sperm count and increase in sperm motility. Thus, it can be stated that both doses possessed the spermatogenic potential, which would be highly beneficial in treating oligospermia or low sperm count. After 54 days of study, there was increase in sperm abnormality (%) at both doses, but not more than 10%, which indicated that this formulation will not induce infertility.

Protective effects of aqueous extract of Solanum nigrum Linn. leaves in rat models of oral mucositis.

Oral mucositis is one of the most debilitating side effects in patient undergoing chemotherapy or chemoradiotherapy. Leaves of the plant Solanum nigrum are used in folklore medicine to treat oral ulcers in India. However, no pharmacological investigation has been carried out till date. Aqueous extract of Solanum nigrum leaves (AESN) was prepared and subjected to various phytochemical screening. HPLC analysis of the ethyl acetate fraction was carried out. The aqueous extract (100 and 200 mg/kg) was further evaluated for its protective effect on two rat models: (a) busulfan plus infrared radiation (chemoradiotherapy) induced oral mucositis and (b) methotrexate (chemotherapy) induced oral mucositis. Various parameters including body weight change, food intake, and mortality were measured. AESN showed protective effect in both models of oral mucositis; however, the higher dose was more effective in chemotherapy induced oral mucositis. A reduction in oral mucositis score (P < 0.05) was observed in the treatment groups. Significant (P < 0.05) improvement in food intake was also observed in AESN treated groups. Aqueous extract of Solanum nigrum leaves has protective effect on chemotherapy and chemoradiotherapy induced oral mucositis in rats.

Bresol inhibits phosphodiesterase 4 gene expression and modulates the levels of select mediators of inflammation in human monocytic cells.

Bresol-a poly-herbal formulation, has been reported to be effective against bronchial asthma and allergic rhinitis in children. In vivo studies have supported the anti-histaminic and anti-anaphylactic action of bresol. However, the mechanism of action of bresol in modulation of inflammation has not been studied at the cellular and molecular level. The present study was aimed to elucidate the mechanism(s) of action of bresol at the cellular and molecular levels, using human monocyte leukemia cells. The effects of bresol on phosphodiesterase 4B (PDE4B) gene expression were analyzed using human monocytic U937 leukemia cells. The ability of bresol to stimulate cAMP formation in these cells, as well as its effects on mediators of inflammation like tumor necrosis factor-α (TNFα), nitric oxide (NO), and cycloxygenase-2 (COX-2) in lipopolysaccharide (LPS)-stimulated U937 cells, were also studied. The results here indicated that bresol exhibited potential anti-inflammatory properties by inhibiting LPS-induced PDE4B gene expression in the cells. Bresol also dose dependently activated cAMP formation, and inhibited TNFα, NO, as well as COX-2 formation in the LPS-stimulated cells. Based upon the results, we concluded that the reported anti-inflammatory activity of bresol might be attributed to its abilities to inhibit PDE4B and thus elevate cAMP levels in human monocytes. The anti-inflammatory effects of bresol might also be a result of the capacity of bresol to modulate the formation of TNFα, NO, and COX-2 in monocytes.

Anti-inflammatory activity of Terminalia paniculata bark extract against acute and chronic inflammation in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Terminalia paniculata Roxb. (Family-Combretaceae) is a wild tree commonly used in traditional ayurvedic medicine for the treatment of inflammation of parotid glands and in menstrual disorders. AIM OF THE STUDY: To explore the folk use of Terminalia paniculata on pharmacological grounds to evaluate the scientific basis of anti-inflammatory activity. MATERIALS AND METHODS: The anti-inflammatory activity of Terminalia paniculata was studied against carrageenan-induced hind paw edema, air pouch inflammation and complete Freund's adjuvant (CFA)-induced arthritis in rats. The aqueous extract of Terminalia paniculata bark (TPW) was administered at the concentrations of 100, 200 and 400mg/kg body weight. RESULTS: TPW showed significant (p<0.05) anti-inflammatory activity by reducing the edema volume in carrageenan-induced paw edema in rats. Further, TPW (400mg/kg) also reduced the carrageenan-induced leukocyte migration (50.92 ± 5.71%) and myeloperoxidase activity (49.31 ± 5.24%) in air pouch exudates. TPW (200mg/kg) exhibits anti-rheumatic and analgesic activities by improving the altered haematological milieu (ESR, CRP, RF, WBC, RBC and Hb) and also by inhibiting the flexion scores and radiographic changes in CFA-induced arthritis. This extract also had significant (p<0.05) effects on the occurrence of secondary lesions compared to CFA control. CONCLUSIONS: Terminalia paniculata bark may be a potential preventive or therapeutic candidate for the treatment of chronic inflammation and arthritis.

Isolation of anxiolytic principle from ethanolic root extract of Cardiospermum halicacabum.

Cardiospermum halicacabum roots have been used traditionally for the treatment of epilepsy and anxiety disorders. The purpose of this study was to characterize the putative phytoconstituents present in the ethanolic root extract having anxiolytic activity using an elevated plus-maze (EPM) and light dark transition model. Control mice were orally treated with an equal volume of vehicle (4% gum acacia), and positive control mice were treated with diazepam (1mg/kg). In the EPM test, out of pool of 19 master fractions (MF) only MF-14, 16 and 17 significantly (30mg/kg, p<0.05, p<0.01 and p<0.001) increased the number of entries in the open arm. MF-14, 16 and 17 (10, 20 and 30mg/kg) had also increased the time spent by mice in illuminated part of the box significantly (p<0.05, p<0.01 and p<0.001), as compared to control. However, significant changes (p<0.05, p<0.01 and p<0.001) were recorded in other parameters, e.g., rearing, time spent in the closed arm and dark zone in both the models. These results suggested that C. halicacabum root is an effective anxiolytic agent. The phytoconstituent responsible for the observed central effects was isolated from MF-14 and identified as well-known compound, Cardiospermin, a cyanogenic glucoside.

Anti-inflammatory properties of Septilin in lipopolysaccharide activated monocytes and macrophage.

In vivo studies have suggested the immunomodulatory properties of Septilin, an herbal preparation. This drug is being used against various types of inflammatory disorders. However, the mechanism of action of Septilin in the modulation of inflammation is not explored using suitable in vitro models. Hence, we decided to study the modulatory role of Septilin in lipopolysaccharide (LPS) mediated signaling in macrophage and monocyte cells. It was observed from the present study that by employing tumor necrosis factor α (TNF-α) bioassay and reverse transcription-polymerase chain reaction (RT-PCR), Septilin inhibited TNF-α production in LPS (1 µg/mL) stimulated RAW 264.7 cells (p < 0.05). 80% inhibition of TNF-α was observed even at 2.5% Septilin. Septilin at all the concentrations tested could also significantly block the LPS mediated nitric oxide (NO) production (p < 0.01) and expression of inducible NO synthase (iNOS) gene. LPS mediated interleukin 6 (IL-6) and IL-8 production was also blocked by Septilin at the concentrations tested. This herbal preparation could also inhibit cycloxygenase 2 (COX-2) activity and suppression of COX-2 and phosphodiesterase 4 B (PDE4B) mRNA expression in a concentration dependent manner. Taken together, these findings from the present in vitro study suggest the anti-inflammatory and immunomodulatory properties of Septilin.