Carissa carandas L. – phyto‐pharmacological review

Antimicrobial Fresh leaf and fruit Chloroform extract followed by ethanol, dichloromethane, acetone, toluene and ethyl acetate Against Styphylococcus aureus species, Klebsiella pneumonia, Escherichia coli; using agar well diffusion assa Among all the extracts, the ethyl acetate possessed most significant results [45 ] Antimicrobial – Methanol Against fungal species Potent effects against fungal strains [46 ] Antimicrobial and antioxidant – Broth ethyl acetate Antimicrobial activity determined against Cryptococcus neoformans, endophytic fungi; total phenolic content determined using Folin–Ciocalteu assay; and antioxidant activity by DPPH assay Broth ethyl acetate extract contained the strongest antimicrobial effect against C. neoformans at MIC of 4 µg/ml and a minimum fungicidal concentration of 8 µg/ml; it possessed highest antioxidant activity with IC50 of 0.03 mg/ml; total phenolic content of 41.20 ± 0.40 mg GAE/g of the extract [47 ] Antimicrobial Leaf and fruit Aqueous and ethanol Against Bacillus cereus (MCCB-0143), S. aureus (MCCB-0139) and E. coli (MCCB-0018) using agar disc diffusion and agar well diffusion Fruit extract resulted highest zone of inhibition (28.0 ± 1.50); strongest antimicrobial effect [48 ] Antimicrobial Fruit Aqueous Using agar plate diffusion method against food pathogenic and spoilage bacteria including Salmonella Typhimurium TISTR 292, S. aureus TISTR 118, E. coli TISTR 780, Aeromonas hydrophila TISTR 1321, Pseudomonas fluorescens TISTR 358 and Bacillus coagulans TISTR 1447 Antimicrobial effect observed in ground pork for prolonged shelf life [49 ] Antimicrobial Fruit Polyphenolic fraction fruits: Terminalia catappa, Carissa carandas and Ziziphus nummularia; spice oil seeds: thymol, mustard, fenugreek and poppy seeds; and herb: green and black teas Against pathogenic bacteria and evaluated minimum inhibitory concentrations Possessed substantial antibacterial effect with MIC 62.5–1000 µg/ml [50 ] Antibacterial Fruit Methanol and aqueous Against Staphylococcus epidermidis, Salmonella paratyphi, B. cereus and Salmonella typhi and determined zone of inhibitions using agar well diffusion method Methanol extract showed high inhibition percentage; aqueous extract exhibited the lowest inhibition percentage against bacterial strains [51 ] Antibacterial Leaf Cold aqueous, methanol, ethanol and ethyl acetate Against Pseudomonas aeruginosa, S. aureus and E. coli using agar well diffusion assay Methanolic, ethyl acetate and ethanolic extracts (concentration of 500 mg/ml) showed inhibitory zone diameter of 23.5, 22.0 and 21.5 mm. Among all extracts, methanol exhibited highest zone of inhibition than that of tetracycline (17.0 mm), standard antibiotic [52 ] Antibacterial Root, leaf and stem Methanol and petroleum ether Using disc diffusion assay against Gram-negative bacteria including E. coli, K. pneumoniae and A. tumifaciens; and Gram-positive bacteria such as S. aureus and B. subtilis; minimum inhibitory (MIC) and minimum bactericidal concentration (MBC) were analysed Leaf and stem extracts possessed significant antibacterial activity against B. subtilis [53 ] Antibacterial and antioxidant Fruit juice Fresh fruit juices (FJS) and freeze-dried fruit juices (FDS) Antioxidant property assessed using DPPH assays; TPC determined using Folin–Ciocalteu reagent; and antibacterial tests evaluated using agar diffusion assay against 10 pathogenic bacteria Both FJS and FDS exhibited broad range of antibacterial activity; FDS slightly decreased the values of DPPH and TPC when compared with FJS [54 ] Antioxidant and DNA damage inhibition in vitro Leaf Methanol TPC determined by Folin–Ciocalteu assay; antioxidant activity studied using DPPH, H2O2 scavenger assay and reducing power activity Significant (P < 0.05) antioxidant effects in a dose-dependent manner, in which DPPH scavenging assay (median inhibitory concentration, 73.1 μg/ml) and H2O2 scavenging activity (median inhibitory concentration, 84.03 μg/ml). It also showed complete protection of pBR322 plasmid DNA from free radical-mediated oxidative stress in a DNA damage inhibition assay [55 ] Antioxidant Fruit Methanol DPPH free radical scavenging activity Methanolic extract exhibited antioxidant effect with IC50 value of 27.45 ± 0.43 µg/ml [21 ] Antioxidant Seed, fruit and leaf. Petroleum ether and methanol FRAP free radical scavenging assay Methanolic leaf extract exhibited highest free radical scavenging property than that of petroleum ether extract of fruit and seed. Antioxidant effect is found high when compared with the standard, ascorbic acid [56 ] Antioxidant Fruit Ethanol and n-hexane DPPH and H2O2 free radical scavenging activity; TPC by Folin–Ciocalteu assay; and determined cytotoxic activities against vincristine sulfate Significant antioxidant activities in both extracts compared to ascorbic acid, ASA and BHT in DPPH assay; higher H2O2 scavenging effect than ASA and BHT; IC50 value of cytotoxic activities for ethanolic and n-hexane extract was found to be 3.43 and 2.66; TPC value 88.3 mg GAE/g extract [33 ] Antioxidant Seed – TPC, FRAP and DPPH free radical scavenging assay, total anthocyanin content, proanthocyanins, ascorbic acid content and tyrosinase inhibitory activities compared with dietary supplement products Significant value of TPC (256.42 mgGAE/g), FRAP (2104.31 µmolFeSO4/g), DPPH (285.06 mgAAE/g) and proanthocyanidins (465.69 mgCE/g). Extract contained highest percentage of tyrosinase inhibition (27.74 mgKAE/g) [57 ] Antioxidant Dried fruits Petroleum ether and methanol DPPH, metal chelating, H2O2 and superoxide assays Methanol extract showed strong antioxidant activities compared with petroleum ether extract [58 ] Antioxidant Fruit Methanol, ethanol and acetone in water as solvent TPC by Folin–Ciocalteu method; TFC by aluminium trichloride method; and DPPH assay 70% acetone extract showed highest % of TPC and antioxidant activity, whereas flavonoid content was found highest in ethanol extract. Significant correlation found between TPC and antioxidant activities [23 ] Antioxidant Fruit – TPC; DPPH, FRAP and chelating effect methods Extract exhibited moderate phenolic content (410 mg/100 g GAE) with marked antioxidant activity (22–64%) [59 ] Antioxidant Fruit and root Chloroform fruit (CFCC) and root (CRCC); ethanolic fruit (EFCC) and root (ERCC) extracts DPPH and nitric oxide radical scavenging assay against BHT EFCC and ERCC contained higher % of TFC and TPC than CFCC and CRCC. All extracts showed potent antioxidant effect, due to the presence of compounds with hydroxyl groups [60 ] Antidiabetic Unripe fruit Methanol and ethyl acetate Against alloxan-induced diabetic rat model Extracts (methanol and ethyl acetate) significantly decreased the elevated blood glucose levels by 48% (P < 0.001) and 64.5% (P < 0.001) at 400 mg/kg, orally, compared to diabetic control [61 ] Antioxidant, antidiabetic and DNA damage inhibition Fruit – In-vitro antioxidant determined by DPPH, FRAP, ABTS and radical cation depolarisation assay; antidiabetic effect evaluated using alpha-glucosidase inhibitory assay Exhibited potent activities [62 ] Antidiabetic Leaf Petroleum ether, methanol and water Against salivary alpha-amylase and starch as substrate using chromogenic DNSA method and starch iodine method Significant inhibition (44.2 ± 1.10%) obtained at 1.5 mg/ml of steroid of leaves (IC50 2.271 g/ml) and 1.5 mg/ml of alkaloids of leaves with % inhibition (43.92 ± 2.68%) (IC50 2.798 g/ml); exhibited potent inhibitory effect [63 ] Antidiabetic Leaf Aqueous Alloxan-induced and normoglycemic Wistar rats. Three different doses such as 250, 500 and 1000 mg/kg administered orally Extract at 500 and 1000 mg/kg showed a significant reduction in the blood glucose levels after an interval of 4, 8 and 24 h in alloxan-induced rats, whereas in case of normoglycemic rats, extract at 1000 mg/kg considerably decreased the blood glucose levels at 8 and 24 h, respectively. [64 ] Antidiabetic, anti-inflammatory and antipyretic Root Ethanol and aqueous Analgesic evaluated using hot plate and acetic acid-induced writhing methods; anti-inflammatory determined against carrageenan-induced paw oedema. Antipyretic activity evaluated by Brewer's yeast-induced pyrexia in rats Attained significant (P < 0.01) analgesic, anti-inflammatory and antipyretic activities at 100 and 200 mg/kg bw; ethanolic extract at 100 mg/kg, b.w. exhibited highest % inhibition of abdominal constriction, that is 72.67% [65 ] Analgesic and antipyretic Leaf Aqueous Using hot plate, acetic acid-induced writhing and yeast-induced hyperthermia methods Significant analgesic and antipyretic activities at all the doses [66 ] Gastroprotectant Leaf Methanolic acetone Using H+/K+ ATPase inhibitory model; TPC and TFC against omeprazole as standard. Extract showed considerable (<0.05) proton-pump inhibitory activity [67 ] Anti-ulcer and antioxidant Leaf 60 % ethanol DPPH free radical scavenging assay; anti-ulcer effect against standard drug, omeprazole Protection index of 42.45%, 47.17% and 64.15% at 100, 200 and 400 mg/kg, respectively. DPPH IC50 values of extract and ascorbic acid were 15.01 µg/ml and 3.56 µg/ml [68 ] Antidiarrhetic Fruit and root Ethanol Castor oil-induced diarrhoea model At 400 mg/kg, ethanol extract of root and fruit attained similar effect as that of loperamide used as standard drug [34 ] Antioxidant, cytotoxic and antineoplastic Leaf Methanol Antioxidant determined using DPPH and ABTS experiments; in- vitro cytotoxic activity evaluated against colonic adenocarcinoma cell lines (SW-480 and SW-48); and in vivo its antineoplastic property tested against Ehrlich ascites carcinoma (EAC) Attained remarkable antioxidant effect using extract that attained significant antioxidant activity tested with DPPH and ABTS assays (IC50 10.5 ± 1.2 and 1.75 ± 0.3 μg/ml) as compared to l-ascorbic acid. In case of cytotoxic study, the extract reduced the viability of adenocarcinoma cells in dose-dependent pattern; in-vivo administration of methanolic extract at 25 mg/kg exhibited significant (P < 0.05) reduction in viable EAC cell count [31 ] Anticancer Seed Methanol Anticancer activity using SRB assay against nine human cancer cell lines from eight different origins namely MCF-7, T-47D (breast), SF-295 (CNS), HCT-116 (colon), A-549 (lung), MDA-MB-435 (melanoma), OVCAR-5 (ovary), PC-3 (prostate) and A-498 (renal) Suppressed the proliferation of human cancer cells with growth inhibition range of 78–100%. It exhibited 100% growth inhibition of A-549 and OVCAR-5 cancer cells and also possessed significant in-vitro cytotoxic effect against lung cancer cells (A-549) [69 ] Neuropharmacological and Diuretic Leaf Methanol Against pentobarbital-induced sleeping time in mice. Diuretic activity examined using the electrolyte loss ratio (Na+/K+ excretion ratio. The standard diuretic furosemide Potentiated the pentobarbital-induced sleeping time in mice; significant diuretic activity at 200 and 400 mg/kg as compared to furosemide [43 ] Antihyperlipidemic Aqueous: ethanol (1:1) Egg yolk-induced hyperlipidemic rats Significant reduction in body weight, cholesterol, triglycerides, HDL and LDL in hyperlipidemic rats comparable to standard drug, atorvastatin [37 ] Proteolytic activity Latex Isolated proteases Caseinolytic, fibrinogenolytic, blood and plasma clot activities Significant proteolytic activity; the enzymes possessed dose-dependent caseinolytic, fibrinogenolytic, blood and plasma clot activities [44 ] Histamine-liberating activity Root Ethanol Using minced guinea-pig lung Possessed the activity [70 ] Anticancer Fruit Dichloromethane and methanol Resazurin microplate assay tested with five cell lines, including KB – oral cavity cancer; MCF7 – breast cancer; NCI-H187 – small lung cancer; HepG2 – hepatocarcinoma; and Caco2 – colon adenocarcinoma cell lines Both extracts not possessed anticancer activity to any cancer cell lines at maximum concentration of 100 µg/Ml [71 ] Adaptogenic Fruit Lanostane triterpenoid isolated from ethanol extract Using anoxia stress tolerance, swimming endurance and cyclophosphamide-induced immunosuppression model. Ethanolic extract (100 and 200 mg/kg per day); lanostane triterpenoid (10 mg/kg per day) Both significantly increased the anoxia stress tolerance, swimming endurance and duration of stay on rotarod and normalised the Hb, RBC, WBC level, altered organ and body weight suppressed by cyclophosphamide [72 ] Anti-inflammatory Root Bioassay-guided fractionation of methanol extract Inhibitory potential towards pro-inflammatory mediators (TNF-α, IL-1β and NO) Attained significant inhibition of NO production comparable to specific NO inhibitor (L-NAME; IC50 = 19.82 ± 1.64 μg/ml) without affecting the cell viability [5 ] Anti-inflammatory and antioxidant activities (in vivo and in vitro) Leaf Naringin (NG) isolated with 80% methanol Anti-inflammatory activity (in vivo) investigated using carrageenan-induced hind rat paw oedema method; antioxidant activity evaluated using superoxide and DPPH radical scavenging assay At 50 and 25 mg/kg, NG showed potent anti-inflammatory effect than that of indomethacin (20 mg/kg) and possessed antioxidant activity [73 ] Anti-inflammatory Dried fruits Methanol Carrageenan-induced hind paw oedema in rats Methanolic fruit extract attained significant activity (P ≤ 0.05) when compared with the control group and exhibited highest % inhibition 76.12% against paw oedema in a dose-dependently [12 ] Anti-inflammatory Immature, mature and ripe fruits Acetone Carrageenan-induced paw oedema in Wistar rats and cotton pellet-induced granuloma Possessed highest % inhibition of inflammation at concentration of 200 mg/kg up to 3 h [74 ] Antioxidant and antiproliferative Fresh ripe fruit Juice and methanol Antioxidative effects evaluated using DPPH and OH scavenging assays. Gallic acid and mannitol used as positive controls. Antiproliferative activity analysed using MTT assay against human cancer cell lines such as KB (human epidermoid carcinoma), MCF-7 (human breast adenocarcinoma), SiHa (human cervical carcinoma) and HepG2 (human hepatocellular carcinoma) cell lines, as well as non-tumorigenic cells; Vero (African green monkey kidney) cell line Both extracts exhibited antioxidative effects in a dose-dependent manner; exhibited weak antiproliferative activity towards any of the cells tested [75 ] Hepatotoxicity Root Ethanol Carbon tetrachloride- and paracetamol-induced hepatotoxicity. 100, 200 and 400 mg/kg, orally Decreased the activities of serum marker enzymes, bilirubin and lipid peroxidation markedly increased the levels of uric acid, glutathione, superoxide dismutase, catalase and protein in a dose-dependent pattern [76 ] Hepatotoxicity Fruit Ethanol Carbon tetrachloride-intoxicated rats. 100, 200 and 400 mg/kg Significantly altered the serum marker levels in hepatotoxic rats [77 ] Hepatotoxicity Leaf Methanol and acetone CCl4-induced hepatotoxicity in albino rats Significant activity as compared to that of silymarin [38 ] Anti-asthmatic Leaf Methanol Using goat trachea model. Different concentrations of extract as 40, 80, 120, 160 and 200 mg/ml Highest anti-asthmatic activity at 200 mg/kg and 62.213% of protection compared with standard chlorpheniramine maleate [78 ] In breast cancer Fruit Ethanol Free radical scavenging and anticancer activity analysed by DPPH and MTT assays; invasive ductal carcinoma breast cancer protein – aromatase was selected as target which is an oestrogen-synthesising enzyme IC50 concentration of extract was 86.7308 (µg/ml) found effective against MCF-7 cell lines [79 ]

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