Toxicological safety assessment of AP-Bio®, a standardized extract of Andrographis paniculata in Sprague Dawley rats.

Andrographis paniculata, commonly known as green chiretta, is a traditionally used plant in India, China, and Southeast Asian countries for its varied health benefits including immune health. The objective of the present study was to assess the safety of AP-Bio®, a standardized A. paniculata extract in Sprague Dawley rats by following the Organisation for Economic Cooperation and Development (OECD) test guidelines of acute and 90-day repeated dose sub-chronic toxicity studies. AP-Bio® did not show any treatment-related clinical signs of toxicity or mortality during the 14-day observation period in animals tested in the single-dose acute oral toxicity study up to a dose of 5000 mg/kg body weight. In the 90-day repeated dose sub-chronic oral toxicity study, no treatment-related adverse clinical signs were observed in any of the treated groups (300, 600, and 900 mg/kg). All treated animals showed usual weight gain and comparable feed intake. The ophthalmoscope examination did not reveal any abnormalities. Also, no toxicologically significant changes were observed in urinalysis, hematology, and blood chemistry parameters. Absolute organ weights and relative organ weights of vital organs did not differ significantly compared to control. Gross and histopathological findings did not show any remarkable and treatment-related changes. Results of the safety evaluation showed the median lethal dose (LD50 ) of AP-Bio® was found to be more than 5000 mg/kg rat body weight and the no observed adverse effect level (NOAEL) of AP-Bio® was found to be 900 mg/kg rat body weight.

Safety of NR-INF-02, an Extract of Curcuma Longa Containing Turmerosaccharides, in Healthy Volunteers: A Randomized, Open-label Clinical Trial.

CONTEXT: Turmeric (Curcuma longa) is a common medicinal plant used in traditional medicine that also has been scientifically validated for its antioxidant, anti-arthritic, anticancer, analgesic, and anti-inflammatory properties. Researchers have still not much explored the beneficial effects of the curcuminoid-free portion of turmeric. NR-INF-02 is a proprietary, patented aqueous extract of Curcuma longa comprising turmerosaccharides with a novel phytochemical composition. OBJECTIVE: The study intended to evaluate the safety and tolerability of NR-INF-02 in healthy adult volunteers at doses of 1000 and 2000 mg, administered for 84 days. DESIGN: The study employed a randomized, open label, two-arm, parallel-group design. SETTING: The trial was carried at 2 sites, the Meenakshi Multispecialty Hospital in Chennai, Tamil Nadu, India and the Vijaya Super Specialty Hospital in Nellore, Andhra Pradesh, India. PARTICIPANTS: Participants were healthy adult, male or female volunteers, aged 18-65 years with a body mass index of ≥18.5 kg/m2 and ≤ 24.9 kg/m2 and a body weight of at least 55 kg for men and 48 kg for women. INTERVENTION: Participants were randomly divided into 2 groups with 24 participants each for a total of 48 participants. They received either 1000 or 2000 mg of NR-INF-02 for 84 days. OUTCOME MEASURES: The incidence of adverse events and the changes from baseline in clinical laboratory parameters-including hematological, biochemical, and urinalysis parameters-were assessed at baseline, at day 42, and postintervention at day 84 as primary endpoints for safety. Secondary endpoints were the changes in vital signs and the difference in the results of an electrocardiogram (ECG) between baseline and days 42 and 84. RESULTS: The NR-INF-02 at doses of 1000 and 2000 mg demonstrated a 4.17% and 20.83% incidence of adverse events (AEs), respectively. The AEs were mild to moderate and were either probably or possibly related, but not definitively, related to treatment. A detailed examination of hematological, biochemical, and urological parameters and of ECG results and vital signs didn't indicate any untoward effects for any participant. CONCLUSION: The study found NR-INF-02 to be safe and tolerable at both tested doses for the given duration of the trial for healthy adult volunteers.

Anti-stress Activity of Ocimum sanctum: Possible Effects on Hypothalamic-Pituitary-Adrenal Axis.

The present study investigated anti-stress potential of Ocimum sanctum in chronic variable stress (CVS) paradigm. Further, the possible mechanism of anti-stress was explored in vitro using cell and cell-free assays. Rats were administered O. sanctum followed by CVS regimen for a period of 16 days. On days 4, 8, 12, and 16, body weight and immobility time in forced swim test were measured. In addition, the possible inhibitory effect of O. sanctum and ursolic acid on cortisol release and CRHR1 receptor activity were studied in cell-based assays, while inhibitory effects on 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) and catechol-O-methyltransferase (COMT) were studied in cell-free assays. CVS group demonstrated less body weight gain and higher immobility time than O. sanctum administered groups, while oral administration of O. sanctum significantly increased body weight gain and decreased the immobility time. Further, O. sanctum and its constituents inhibited cortisol release and exhibited a significant CRHR1 receptor antagonist activity. Also, they had specific inhibitory activity towards 11ß-HSD1 and COMT activity. Thus, O. sanctum was found to be effective in the management of stress effects, and anti-stress activity could be due to inhibition of cortisol release, blocking CRHR1 receptor, and inhibiting 11ß-HSD1 and COMT activities. Copyright © 2016 John Wiley & Sons, Ltd.

Erectogenic and Aphrodisiac Property of Moringa oleifera: Involvement of Soluble Epoxide Hydrolase Enzyme.

Soluble epoxide hydrolase (sEH) inhibitors have been reported to improve penile erection; therefore, sEH could be useful for management of erectile dysfunction. Methanolic and aqueous extracts of 30 Indian medicinal plants were screened for their sEH inhibition potential. Fifteen extracts showed >50% inhibition when screened at 50 µg/mL in sEH inhibition assay. Methanolic extract of Moringa oleifera Lam. (Moringaceae) seeds (MEMO) was most potent with IC50 1.7 ± 0.1 µg/mL and was selected for in vitro studies on isolated rat corpus cavernosum smooth muscle and in vivo sexual behaviour studies on healthy and diabetic rats. Rats were divided into five groups, each containing six animals and treated orally with either water, vehicle (1% Tween-20), MEMO (45 and 90 mg/kg/day for 21 days), and standard drug, sildenafil (5 mg/kg/day for 7 days). An equal number of female rats were used, and the effect of MEMO and sildenafil was compared with that of vehicle. MEMO significantly relaxed isolated rat corpus cavernosum smooth muscle at 0.1-100 µg/mL in vitro and significantly increased (p < 0.05) sexual activity, intracavernous pressure/mean arterial pressure in normal and diabetic rats. The increase in erectile function of rats by MEMO could be because of its sEH inhibitory activity. Copyright © 2016 John Wiley & Sons, Ltd.

Aldose reductase and protein tyrosine phosphatase 1B inhibitory active compounds from Syzygium cumini seeds.

CONTEXT: Syzygium cumini (L.) Skeels (Myrtaceae), commonly known as jamun, is an Indian plant, traditionally well known for its medicinal properties including antidiabetic activity. OBJECTIVE: To isolate the antidiabetic compounds from Syzygium cumini seeds and evaluate their activity using aldose reductase (AR) and protein-tyrosine phosphatase 1B (PTP1B) inhibition assays. MATERIALS AND METHODS: The dried seeds were extracted with methanol and partitioned with ethyl acetate, butanol, and water. The extracts were screened for antidiabetic activity at a concentration of 100 µg/mL using in vitro AR and PTP 1B inhibition assays. RESULTS AND DISCUSSION: The highly enriched fractions obtained from broad ethyl acetate fraction yielded maslinic acid (1), 5-(hydroxymethyl) furfural (2), gallic acid (3), valoneic acid dilactone (4), rubuphenol (5), and ellagic acid (6). Structures were elucidated by (1)H-NMR and (13)C-NMR. The initial ethyl acetate fraction showed AR inhibitory activity with the IC50 value of 2.50 µg/mL and PTP1B enzyme inhibition with the IC50 value of 26.36 µg/mL. Compounds 3, 4, 5, and 6 were found to inhibit AR with IC50 values of 0.77, 0.075, 0.165, and 0.12 µg/mL while the compounds 4, 5, and 6 inhibited PTP1B with IC50 values of 9.37, 28.14, and 25.96 µg/mL, respectively. CONCLUSION: The results of this study demonstrate that the isolated constituents show promising in vitro antidiabetic activity and, therefore, can be candidates for in vivo biological screening using relevant models to ascertain their antidiabetic activity.

Anticancer activity of Bacopa monnieri through apoptosis induction and mitophagy-dependent NLRP3 inflammasome inhibition in oral squamous cell carcinoma.

BACKGROUND: Bacopa monnieri (BM) is traditionally used in human diseases for its antioxidant, anti-inflammatory and neuroprotective effects. However, its anticancer potential has been poorly understood. AIM: The aim of this study was to explore the detailed anticancer mechanism of BM against oral cancer and to identify the bioactive BM fraction for possible cancer therapeutics. RESULTS: We performed bioactivity-guided fractionation and identified that the aqueous fraction of the ethanolic extract of BM (BM-AF) had a potent anticancer potential in both in vitro and in vivo oral cancer models. BM-AF inhibited cell viability, colony formation, cell migration and induced apoptotic cell death in Cal33 and FaDu cells. BM-AF at low doses promoted mitophagy and BM-AF mediated mitophagy was PARKIN dependent. In addition, BM-AF inhibited arecoline induced reactive oxygen species production in Cal33 cells. Moreover, BM-AF supressed arecoline-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation through mitophagy in Cal33 cells. The in vivo antitumor effect of BM-AF was further validated in C57BL/6J mice through a 4-nitroquinolin-1-oxide and arecoline-induced oral cancer model. The tumor incidence was significantly reduced in the BM-AF treated group. Further, data obtained from western blot and immunohistochemistry analysis showed increased expression of apoptotic markers and decreased expression of inflammasome markers in the tongue tissue obtained from BM-AF treated mice in comparison with the non-treated tumor bearing mice. CONCLUSION: In conclusion, BM-AF exhibited potent anticancer activity through apoptosis induction and mitophagy-dependent inhibition of NLRP3 inflammasome activation in both in vitro and in vivo oral cancer models. Moreover, we have investigated apoptosis and mitophagy-inducing compounds from this plant extract having anticancer activity against oral cancer cells.

Ocimum tenuiflorum extract (HOLIXERTM): Possible effects on hypothalamic-pituitary-adrenal (HPA) axis in modulating stress.

Ocimum tenuiflorum is a sacred medicinal plant bestowed with multiple health benefits. This plant is traditionally considered an adaptogen. Many scientific studies have indicated the anti-stress potential of Ocimum tenuiflorum but with higher doses. The present study investigated the effects of HolixerTM (a clinically studied standardized Ocimum tenuiflorum extract) on modulating stress using two in vivo models, namely the swim endurance study in mice and forced swim test in rats. In addition, we explored the mechanism of action of HolixerTM on the HPA axis using two in vitro cell-based assays to check for its inhibitory effect on cortisol release and CRF1 receptor antagonistic activity. Ocimum tenuiflorum extract enhanced the swimming time in mice, reduced the stress-induced increase in immobility time, and prevented the increase in corticosterone in rats subjected to the forced swim test. Further, Ocimum tenuiflorum extract inhibited cortisol release and exhibited a significant CRF1 receptor antagonist activity. Thus, Ocimum tenuiflorum extract was found effective in managing stress, and the effect could be due to the inhibition of cortisol release and the antagonistic effect on the CRF1 receptors.

Acute and Subchronic Toxicity Study of Flavonoid Rich Extract of Glycyrrhiza glabra (GutGard®) in Sprague Dawley Rats.

Glycyrrhiza glabra (G. glabra) is well known for its health benefits based on the traditional and current scientific evidence. The aim of the present study was to evaluate the safety of GutGard, a standardised-flavonoid rich extract of G. glabra. The study was designed to evaluate the acute and subchronic oral toxicity of GutGard in Sprague Dawley rats according to the procedures and methods of Organisation for Economic Cooperation and Development (OECD) test guidelines for acute and subchronic toxicity. A single dose of GutGard at 5000 mg/kg body weight did not produce treatment related clinical signs of toxicity or mortality in any of the animals tested during the 14-day observation period. Therefore, the median lethal dose was estimated to be more than 5000 mg/kg. A subchronic oral toxicity study for 90 days in rats at the dose levels of 250, 500, and 1000 mg/kg did not show any treatment related adverse clinical signs. The treated animals exhibited normal weight gain and comparable feed intake. Ophthalmoscope examination did not reveal any abnormalities. Further, GutGard administration in rats did not show any clinical evidence of toxicity with respect to urinalysis, haematology, and blood chemistry parameters. The relative organ weight of vital organs did not differ significantly as compared to control. Gross and histopathological findings did not show any remarkable and treatment related changes. Based on the current experimental study findings, the median lethal dose (LD50) of GutGard was found to be >5000 mg/kg b.wt and the no observed adverse effect level (NOAEL) was found to be 1000 mg/kg rat b.wt.

A flavonoid rich standardized extract of Glycyrrhiza glabra protects intestinal epithelial barrier function and regulates the tight-junction proteins expression.

BACKGROUND: Intestinal epithelial barrier dysfunction predisposes to many gastrointestinal, metabolic, and psychological disorders. A flavonoid rich extract of Glycyrrhiza glabra (FREG) has previously been reported to possess anti-inflammatory, antioxidant, and antiulcer properties. AIM: To investigate the effect of FREG (GutGard®) on restoring intestinal barrier function in tumor necrosis factor-alpha (TNF-α) stimulated human colonic adenocarcinoma cell monolayer (Caco-2) and 2,4,6-Trinitrobenzenesulfonic acid (TNBS) induced ulcerative colitis in rats. METHODS: In in vitro, human intestinal Caco-2 cell monolayers were treated with TNF-α in the presence or absence of FREG and the paracellular permeability to FITC-conjugated 4-kD dextran (FD4) was measured to evaluate protection against the barrier dysfunction. In in vivo, intestinal barrier dysfunction was induced in male albino Wistar rats via intrarectal instillation of TNBS. Subsequently, the rats were treated orally with either FREG at 6.25, 12.5, and 25 mg/kg body weight, or Mesacol (250 mg/kg) for 5 days. On day 5, intestinal epithelial permeability was assessed with FD4 leakage into the serum. Also, colonic inflammation, colon morphology, histology and macroscopic score, weight to length ratio were evaluated. The activity of myeloperoxidase (MPO), TNF- α, secretory IgA levels and tight junction proteins expression were evaluated in rat's colon. RESULTS: FREG protected the intestinal epithelial barrier integrity in human intestinal Caco-2 cells in vitro. FREG administration significantly improved the intestinal epithelial barrier function as evident from significant reduction in FD4 leakage. The colon morphology, histology score, macroscopic score, colon weight to length ratio also indicates beneficial effects of FREG on barrier function. In addition, FREG regulated the tight junction proteins, and markedly decreased TNF-α, MPO levels and significantly increased the secretory IgA levels in TNBS induced colitis rats. CONCLUSION: The study findings support the protective action of FREG on intestinal epithelial barrier integrity indicating its potential in protecting from implications of leaky gut.

Safety Evaluation of Standardized Extract of Curcuma longa (NR-INF-02): A 90-Day Subchronic Oral Toxicity Study in Rats.

NR-INF-02 is a standardized extract containing turmerosaccharides from Curcuma longa that has anti-inflammatory, analgesic, and chondroprotective potential. In view of its potential uses, NR-INF-02 was evaluated for its safety in Wistar rats at an oral dose of 250, 500, and 1000 mg/kg in a 90-day repeated dose subchronic toxicity study. NR-INF-02 administered at 250, 500, and 1000 mg/kg for 90 days did not show any mortality or clinical signs of toxicity. Body weight gain, food consumption, ocular and neurological examination, and hematological, blood biochemical, hormone, and urine analysis revealed no evidence of toxicity of NR-INF-02 treatment in rats. Absolute and relative organ weights were comparable to control rats. The study did not reveal any major treatment related gross pathological and histopathological alterations in the tissues or organs examined. Thus, based on study observations, the no-observed adverse effect level (NOAEL) was found to be 1000 mg/kg body weight in albino Wistar rats.

Aminoglycosides can be a better choice over macrolides in COVID-19 regimen: Plausible mechanism for repurposing strategy.

In the current COVID-19 pandemic, prioritizing the immunity enhancers is equally important to anti-virals. Defensins are the forgotten molecules that enhance the innate immunity against various microbes. Although macrolides like azithromycin and clarithromycin etc., have been reported to act against respiratory infections but they lack the ability of immunity enhancement through defensins. The aminoglycosides were proved to have defensin mediated antiviral activity, that could enhance the immunity. So, Consideration of aminoglycosides can be a double edge sword viz., against respiratory infection as well as Immunity enhancer (along with anti-virals) for COVID-19 regimen.

Anti-diarrhoeal activity of a polyherbal formulation in rats and elucidation of its cellular mechanisms.

OBJECTIVE: The present study was aimed to study anti-diarrhoeal activity of a polyherbal formulation (PHF) in rats and elucidate its mechanism of action. MATERIALS AND METHODS: Anti-diarrhoeal activity of PHF was investigated using castor oil-induced diarrhoea, small intestinal transit and enteropooling models in rats. PHF was tested at 75, 150 and 300 mg/kg rat body weight. Loperamide was used as a reference control for in vivo studies. Anti-secretory action was evaluated against heat labile enterotoxin (from Escherichia coli) induced secretion in rat ileal loop model. The effect of PHF (12.5-100 µg/ml) on cAMP-dependent secretory activity was investigated against forskolin-induced cAMP release in HT-29 cells. RESULTS: PHF demonstrated significant (p≤0.05) anti-diarrhoeal activity by increasing the time for first faecal drop and inhibited diarrhoeal episodes by 43, 58 and 60% at 75, 150 and 300 mg/kg body weight, respectively in a dose-dependent manner. Also, the intestinal transit was inhibited upto 33% and the weight of secretory contents induced by castor oil was significantly reduced by PHF, approximately 29% in enteropooling assay. On the other hand, the intestinal loop instilled with PHF and enterotoxin from E. coli demonstrated 61% inhibition of fluid accumulation as compared to loop instilled with enterotoxin only. In vitro studies indicated that PHF inhibits cAMP release in HT-29 cells corroborating the anti-secretory effects observed in aforesaid studies. CONCLUSION: The results suggest that the PHF possesses anti-diarrhoeal activity, evident through reduced faecal output, decreased intestinal transit and anti-secretory activities.

A Perspective on Additional Approaches Beyond Organic Marker Compounds While Developing Analytical Monographs for Botanicals.

Most of the Pharmacopoeia and other monographs that provide the quality specifications for botanicals typically contain identification and physicochemical tests, assays, and limits for contaminants. The assay methods generally involve quantitative determination of known organic compounds, commonly known as markers. The authors explore and propose that there is a need for additional approaches beyond markers, especially for botanicals derived from traditional knowledge and use. Preliminary data on few selected botanicals are additionally provided to communicate the thought process.

In vitro Evaluation of Antioxidant Potential of Isolated Compounds and Various Extracts of Peel of Punica granatum L.

BACKGROUND: Punica granatum L. (Lythraceae) peel has been proven to exhibit widespread pharmacological application against multitude of diseases due to the presence of bioactive principles. OBJECTIVE: The objective is to isolate the bioactive compounds from the pericarp of P. granatum and to evaluate the antioxidant activity of various extracts. MATERIALS AND METHODS: Dried peel of P. granatum was extracted with aqueous acetone and chromatographed on Diaion HP-20. Enriched fractions were rechromatographed on Sephadex LH-20 and purified on preparative high-performance liquid chromatography to identify individual compounds. The dried peel was extracted with different solvents to evaluate the antioxidant activity of the extracts. RESULTS: On the chemical investigation, three compounds were isolated and characterized as punicalagin, 2,3-(S)-hexahydroxydiphenoyl-D-glucose, and punicalin, using various spectroscopic techniques. CONCLUSION: Results indicate that the isolated compounds have possessed antioxidant activity, and aqueous, methanol, and aqueous acetone extract showed significant scavenging of 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) radicals. SUMMARY: In vitro antioxidant activity of Punica granatum extracts was evaluated by 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) assayDried peel of P. granatum was extracted with different solvents to evaluate the antioxidant activity of the extractsAqueous acetone extract was found to be most active and chromatographed further to afford punicalagin, 2,3-(S)-hexahydroxydiphenoyl-D-glucose, and punicalinThe presence of antioxidant properties of three compounds in the peel of P. granatum has been demonstrated. Abbreviations Used: HPLC: High-performance liquid chromatography; HHDP: Hexahydroxydiphenoyl; DPPH: 2,2-diphenyl-1-picrylhydrazyl; ABTS: 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid); UV: Ultraviolet; PDA: Photodiode array; LC: Liquid chromatography; NMR: Nuclear magnetic resonance; MHz: Megahertz; w/v: Weight by volume; MS: Mass spectra.

Effects of turmeric curcuminoids and metformin against central sensitivity to pain in mice.

The reported experimental study was conducted to compare the effects of repeated daily oral doses of curcuminoids (CLE) with metformin as potential antidepressants and analgesics. Effects of a single and ten daily oral doses of CLE (5, 20, 80 mg/kg/day) and of 50 mg/kg/day metformin (MET) were compared in mice hot plate test (HPT) for analgesics. On the 11th treatment day, all animals were subjected to foot shock stress triggered hyperthermia test, and on the 12th treatment day to tail suspension test (TST) for antidepressants. Immediately thereafter, their blood levels of glucose, insulin and cortisol were quantified. Dose dependent analgesic activity of CLE was observed in HPT, whereas the metformin dose tested suppressed only pain hypersensitivity in the test. But statistically significant effects of both of them were observed in TST, and both of them also afforded protections against body weight loss and slight elevation in core temperatures induced by daily handling and repeated testing. CLE or metformin had no significant effects in foot shock stress triggered transient hyperthermic responses or on blood glucose, insulin and cortisol levels. Reported results reveal that curcuminoids as well as metformin are stress response modifiers with antidepressants like activities, but only low dose curcuminoids possess centrally acting analgesics like activities. They suggest that the bio-assay system used in this study is well suited for identifying curcuminoids like plant metabolites with analgesic and anti-stress activities, and that low dose curcuminoids are more effective as analgesics than low dose metformin.

Bioactive Turmerosaccharides from Curcuma longa Extract (NR-INF-02): Potential Ameliorating Effect on Osteoarthritis Pain.

BACKGROUND: Curcuma longa has long history of medicinal use in Ayurveda. A unique product NR-INF-02 was prepared from C. longa that was standardized to contain turmerosaccharides. OBJECTIVE: The present study investigated the effect of turmerosaccharides rich fraction of NR-INF-02 on monosodium iodoacetate (MIA)-induced OA pain animal model that mimics human OA. Further, the analgesic effect of turmerosaccharides rich fraction was compared to turmerosaccharides less fraction of NR-INF-02. MATERIALS AND METHODS: OA pain was chemically induced by intra-articular administration of single dose of 25 µl of 0.9% saline containing 0.3 mg MIA into the right knee of male albino Wistar rat. Turmerosaccharides rich fraction and turmerosaccharides less fraction (at 22.5, 45 and 90 mg/kg rat body weight dose levels) were administered as a single dose orally on day 5 of post-MIA injection. OA pain was measured using hind limb weight-bearing ability at 1, 3, 6, and 24 h post-test substance administration on day 5. RESULTS: Oral administration of turmerosaccharides rich fraction and turmerosaccharides less fraction (at 45 and 90 mg/kg) although significantly decreased the OA pain at all the intervals, the effect of turmerosaccharides rich fraction (57%) on OA pain was superior to turmerosaccharides less fraction (35%). CONCLUSION: Bioactive turmerosaccharides from C. longa extract contribute to the observed anti-arthritic effect in rats. SUMMARY: Osteoarthritic pain was induced by intra-articular injection of MIA into the right kneeSingle administration of TRF/TLF on day 5 resulted in dose-dependent significant reduction of OA painTRF showed better analgesic activity than TLFTRF at 45 and 90 mg/kg has similar effects on OA pain as that of tramadolTurmerosaccharides identified as bioactive constituents of C. longa extract. Abbreviations used: MIA: Monosodium iodoacetate; i.ar: Intra-articular; OA: Osteoarthritis; TRF: Turmerosaccharides rich fraction; TLF: Turmerosaccharides less fraction; PGE2: Prostaglandin E2; ROS: Reactive oxygen species.

Evaluation of Cholesterol-lowering Activity of Standardized Extract of Mangifera indica in Albino Wistar Rats.

INTRODUCTION: Cholesterol lowering activity of Mangifera indica L. has been determined by earlier researchers and kernel, leaf and bark have shown significant activity. However, the specific cholesterol lowering activity of leaf methanol extract has not been determined. MATERIALS AND METHODS: The present study involved evaluation of cholesterol lowering potential of methanol extract of M. indica leaves using high cholesterol diet model in albino Wistar rats. The acute oral toxicity at a dose of 5000 mg/ kg body weight was also determined in female albino Wistar rats. Phytoconstituents Iriflophenone 3-C-ß-D-glucoside and mangiferin were quantified in methanol extracts of different varieties of mango leaves using high performance liquid chromatography. RESULTS AND DISCUSSION: Significant cholesterol lowering activity was observed with methanol extract of M. indica leaves, at dose of 90 mg/kg body weight in rats and it was also found to be safe at dose of 5000 mg/kg rat body. Iriflophenone 3-C-ß-D-glucoside and mangiferin were found to be in the range of 1.2 to 2.8% w/w and 3.9 to 4.6% w/w, respectively which along with 3 ß taraxerol and other sterols could be contributing to the cholesterol lowering activity of mango leaves extract. CONCLUSIONS: The phytosterols rich extract of Mangifera indica leaves is a good source of nutraceutical ingredient that have the potential to lower serum cholesterol levels. SUMMARY: The Mangifera indica leaves methanolic extract showed significant cholesterol lowering activity in high cholesterol diet induced hypercholesterolaemia model in rats when evaluated at a dose of 90 mg/kg rat body weight. The extract was found to contain Iriflophenone 3-C-ß-D-glucoside and mangiferin which along with 3 ß taraxerol and other sterols could be contributing to the cholesterol lowering activity.

Is Andrographis paniculata extract and andrographolide anaphylactic?

Andrographis paniculata, "King of bitters" is a popularly known medicinal plant extensively used in many parts of the world for treatment of various diseases. Since recent past, anaphylactic/allergic type adverse events were reported upon A. paniculata usage, the study aimed to evaluate the anaphylactic and anaphylactoid potential of A. paniculata extract and andrographolide (a major phytoactive of A. paniculata). The anaphylactic potential was evaluated using active systemic anaphylaxis (ASA) assay in guinea pigs. Further, the release of allergic mediators was measured in immunoglobulin E (IgE) sensitized and non-IgE sensitized Rat Basophilic Leukemia (RBL-2H3) cell lines in-vitro. A. paniculata extract or andrographolide sensitized guinea pigs following the challenge antigen administration orally and intravenously did not demonstrate any clinical signs of anaphylaxis. IgE sensitized and non- IgE sensitized RBL-2H3 cells treated with A. paniculata extract did not induce release of allergic mediators. Whereas IgE sensitized and non- IgE sensitized RBL-2H3 cells treated with andrographolide demonstrated mild to moderate release of allergic mediators. A. paniculata extract has no anaphylactic and anaphylactoid potential in in-vivo and in-vitro studies. Whereas, andrographolide effects on allergic mediators in in-vitro studies needs to be scrutinized if they are of biologically important.

Anti-Inflammatory Activity of Polysaccharide Fraction of Curcuma longa Extract (NR-INF-02).

The aim of the study was to investigate the safety and anti-inflammatory effects of polysaccharide fraction (F1) of Curcuma longa extract (NR-INF-02) in classical rodent models of inflammation. F1 was evaluated for its acute oral toxicity and found to be safe upto 5000 mg/kg body weight in rats. The anti-inflammatory activity of F1 was evaluated in acute (carrageenan - induced paw edema; xylene - induced ear edema) and chronic (cotton pellet - induced granuloma) models of inflammation. The results of the study demonstrated that F1 significantly (p ≤ 0.05) inhibited carrageenan-induced paw edema at 1 h and 3 h at doses of 11.25, 22.5 and 45 mg/kg body weight in rats. Also, F1 at doses of 15.75, 31.5 and 63 mg/kg significantly inhibited the xylene induced ear edema in mice. In a chronic model, F1 at 11.25, 22.5 and 45 mg/kg doses produced significant reduction of wet and dry weights of cotton pellets in rats. Overall results indicated that F1 of NR-INF-02 significantly attenuated acute and chronic inflammation in rodent models. This study emphasizes on the importance of Curcuma longa polysaccharide's role in acute and chronic inflammation.

Cholesterol esterase inhibitory activity of bioactives from leaves of Mangifera indica L.

BACKGROUND: In the earlier studies, methanolic extract of Mangifera indica L leaf was exhibited hypocholesterol activity. However, the bioactive compounds responsible for the same are not reported so far. OBJECTIVE: To isolate the bioactive compounds with hypocholesterol activity from the leaf extract using cholesterol esterase inhibition assay which can be used for the standardization of extract. MATERIALS AND METHODS: The leaf methanolic extract of M. indica (Sindoora variety) was partitioned with ethyl acetate and chromatographed on silica gel to yield twelve fractions and the activity was monitored by using cholesterol esterase inhibition assay. Active fractions were re-chromatographed to yield individual compounds. RESULTS AND DISCUSSION: A major compound mangiferin present in the extract was screened along with other varieties of mango leaves for cholesterol esterase inhibition assay. However, the result indicates that compounds other than mangiferin may be active in the extract. Invitro pancreatic cholesterol esterase inhibition assay was used for bioactivity guided fractionation (BAGF) to yield bioactive compound for standardization of extract. Bioactivity guided fractionation afford the active fraction containing 3b-taraxerol with an IC50 value of 0.86µg/ml. CONCLUSION: This study demonstrates that M. indica methanol extract of leaf have significant hypocholesterol activity which is standardized with 3b-taraxerol, a standardized extract for hypocholesterol activity resulted in development of dietary supplement from leaves of Mangifera indica.