Partially purified lead molecules from Dodonaea viscosa and their antimicrobial efficacy against infectious human pathogens.

BACKGROUND: The utilization of medicinal plants and their drugs have the advantage of reducing side effects compared with manufactured antimicrobials. Artificial drugs have unpleasant side effects, further, the number of drug resistant pathogens is increasing, thus huge challenge for control of resistant pathogens. Therefore, the current research explores the potential of partially purified bioactive compounds from Dodonaea viscosa against certain human pathogens. METHODS: Healthy leaves of D. viscosa (L.) were collected, extracted and optimized with different solvents. Preliminary phytochemical screening of the extracts was done and antibacterial activities were tested against human pathogens. The active crude extract was further purified by column chromatography and the homogeneity was confirmed by thin layer chromatography (TLC). The partially purified compounds were screened further for antibacterial, antibiofilm and anticancer activities. RESULTS: The crude ethanol extract of D. viscosa leaves showed the presence of phytochemical like tannins, alkaloids, flavanoids, terpenoids, glycosides, steroids and phenols. Ethanol extract exhibited the maximum zone of inhibition (11 mm) against S. agalactiae, B. cereus, S. typhi and E. coli at 15 mg when compared with other bacteria. Column chromatography fractions Dv12 and Dv20 exhibited the maximum zone of inhibition against B. cereus. 1000 µg of Dv12 partially purified compound against streptococcus isolates in glass test tube showed biofilm inhibition range of 34.4%-63.1%. Whereas B. cereus, S. aureus, S. typhi, and K. pneumoniae showed 31.1%-53.6% biofilm inhibition compared to curcumin control. Active fractions of Dv12 and Dv20 increased concentration confirmed that the gradual decrease in cell density and possesses growth inhibition towards A 549 human lung adenocarcinoma cells. CONCLUSION: We have extracted the bioactive compounds from D. viscosa (L.) leaves and tested the activity of a partially purified compound against human pathogenic bacteria, biofilm formation and cytotoxicity against A 549 human lung adenocarcinoma cells. The purified bioactive compounds might be used as therapeutic agents against different microbial infections such as skin infection, throat infection and other infectious diseases.

Nephroprotective effect of pigmented violacein isolated from Chromobacterium violaceum in wistar rats.

The present study aimed to analyze the nephroprotective property of violacein obtained from the bacterium, Chromobacterium violaceum. The nephrotoxicity in the animal model was induced by gentamicin, potassium dichromate, mercuric chloride, and cadmium chloride-induced nephrotoxicity in the Wistar rats was analyzed by measuring the serum creatinine, uric acid, and urea level. The present investigation revealed the nephroprotective property on convoluted proximal tubule (S1 and S2 segments) and the straight proximal tubule (S3 segment). Also, violacein significantly improved the renal function by the renal protective property on S2 segment of proximal tubule from the nephrotoxicity stimulated by mercuric chloride, potassium dichromate, cadmium chloride and gentamicin in animal models. Animal model studies revealed that violacein at 20 and 40 mg/kg p.o improved the renal function and significantly reduced the increased amount of uric acid, creatinine, and blood urea compared to the control.

Discovery of novel cage-like heterocyclic hybrids as anti-inflammatory agents through the inhibition of nitrite, PGE2 and TNF-α.

Novel cage-like indolizine-acenaphthene-pyridinone heterocyclic hybrids were synthesized in good yields through [bmim]Br mediated tandem 1,3-dipolar cycloaddition-annulation sequence. The anti-inflammatory activity of these hybrids was performed using carrageenan-induced hind paw oedema, croton oil-induced ear oedema and cotton pellet-induced granuloma models. Four of these cage-like heterocyclic hybrids viz. 4b, 4d, 4e and 4j showed substantial anti-inflammatory activities against acute and chronic inflammatory models and also showed significant inhibition of PGE2, TNF-α, and nitrite levels in carrageenan-induced hind paw oedema.

A competent synthesis and efficient anti-inflammatory responses of isatinimino acridinedione moiety via suppression of in vivo NF-κB, COX-2 and iNOS signaling.

A potent Nonsterodial Anti-inflammatory Drug (NSAID) candidates has been conceived and built by an assembly of a hydrophilic, fluorescent and COX-2 inhibiting units in the same molecule. The isatinimino-acridinedione core (TM-7) was achieved in a simple three step synthetic procedure viz (i) a multicomponent reaction between dimedone, aldehyde and amine to furnish the nitroacridinedione (4), (ii) reduction step and (iii) schiff's-base condensation with isatin. The excellent anti-inflammatory pharmacological efficiency of the drug was established by in vivo biological experiments. Accordingly, it was found that the treatment with the synthesized isatinimino analogues (dosage: 30 mg/kg) inhibited protein expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB) as well as production of prostaglandin E2 (PGE2), nitric oxide (NO), tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1ß), and interleukin-6 (IL-6) levels induced by carrageenan. Further, a comparative molecular modeling analysis of TM-7 carried out with the crystal structure of aspirin acetylated human COX-2 suggested effectively binding and efficient accommodation inside the active site's gorge.

Spirulina consumption effectively reduces anti-inflammatory and pain related infectious diseases.

BACKGROUND: Inflammation and pain triggers several pathological illnesses. Synthetic drugs used for the controlling of inflammatory conditions convey significant toxic effects. Global scientific community continually attempt to improve effective, economic and harmless naturally derived remedies against inflammation and pain. The present study aimed to quantify the phytochemical constituents of the freshly cultivated Spirulina and targeted to examining the anti-inflammatory and analgesic activity of Spirulina extract (SE) derived from Arthrospira platensis. METHODS: The anti-inflammatory effect of SE was evaluated in animal models including carrageenan-induced rat hind paw oedema, and cotton pellet-induced granuloma formation. Analgesic effects of SE were evaluated by acetic acid induced writhing response and hot plate test. RESULTS: Phytochemical quantification guided to identify seven carbohydrates, thirteen amino acids, eleven fatty acids and polyphenolic compounds respectively. The results indicated that SE significantly attenuated carrageenan-induced hind paw oedema, and cotton pellet-induced granuloma. Preliminary molecular mechanistic studies established that SE decreased the productions of TNF-α, IL-1ß, IL-6, PGE2 and NO, and suppressed the activities of COX-2 and iNOS. CONCLUSION: These results provide a strong scientific foundation for the anti-inflammatory and analgesic activities of SE against different studies in animal models.

Anti-inflammatory activity of rhein isolated from the flowers of Cassia fistula L. and possible underlying mechanisms.

OBJECTIVE: Anti-inflammatory activity of rhein in animal models with potential mechanism of actions. METHODS: Rhein was isolated from Cassia fistula L. flowers collected in Chennai, Tamil Nadu, India. Its anti-inflammatory activity was then investigated in Wistar rats and mice using carrageenan-induced hind paw oedema, croton oil-induced ear oedema, cotton pellet-induced granuloma and acetic acid-induced vascular permeability models. RESULTS: Administration of rhein (10, 20, 40 mg/kg) significantly (p < 0.05) inhibited carrageenan-induced paw oedema in rats and croton oil-induced ear oedema in mice in dose-dependent manners. Continual administration of rhein to rats using implanted cotton pellets significantly (p < 0.05) reduced granuloma formation (20 mg/kg: 17.24%; 40 mg/kg: 36.12%) compared to control group animals. Administration of rhein increased the activities of catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) and decreased the levels of nitrite, interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), malondialdehyde (MDA) and vascular endothelial growth factor (VEGF) compared to control animals. Western blotting results revealed that rhein diminished carrageenan-induced cyclooxygenase (COX)-2 and inducible nitric oxide synthase (iNOS) and increased heme oxygenase (HO)-1, nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPAR)-γ and heat shock protein (HSP)-72 expression after 6 h in the paw oedema model. CONCLUSION: The anti-inflammatory mechanisms of rhein might be related to decrease in the levels of MDA, iNOS and COX-2 and the stimulation of HO-1, PPAR-γ and Nrf2 expression via increases in the activities of CAT, SOD and GSH-px through the suppression of nitrite, TNF-α, IL-6 and IL-1ß.

Functionalized spirooxindole-indolizine hybrids: Stereoselective green synthesis and evaluation of anti-inflammatory effect involving TNF-α and nitrite inhibition.

Stereoselective synthesis of a small library of novel spiroheterocyclic hybrids including indolizine, oxindole, and substituted piperidine units has been accomplished in [bmim]Br using a [3 + 2] cycloaddition strategy in good yield and were tested for their anti-inflammatory activities. The effects of compounds (4a-o) against inflammation were studied using carrageenan-induced hind paw oedema, croton oil-induced ear oedema, and cotton pellet-induced granuloma models. Among the heterocyclic hybrids, compounds 4d, 4g, and 4o showed significant anti-inflammatory activities against acute and chronic inflammatory models. These compounds also showed significant inhibition of PGE2, TNF-α, and nitrite levels in carrageenan-induced hind paw oedema. Thus it is evident from our study that these novel spiroheterocyclic hybrids 4d, 4g, and 4o displayed significant anti-inflammatory effects that involve the reduction of PGE2, TNF-α, and nitrite levels.

Variation of glucosinolates on position orders of flower buds in turnip rape (Brassica rapa).

To glucosinolate (GSL) contents on flower buds depending on their position orders in turnip rape (Brassica rapa), three Japanese 'Nabana' cultivars such as cv. No. 21 (Brassica rapa, early type), cv. Husanohana (B. rapa, late type) and cv. Norin No. 20 (B. napus) were investigated using HPLC analysis. Ten GSLs including glucoraphanin, sinigrin, glucoalyssin, napoleiferin, gluconapin, 4-hydroxyglucobrassicin, glucobrassicanapin, glucobrassicin, and gluconasturtiin were detected. Differences in individual and total GSL contents were found between two plant varieties, which are also depending on various developmental stages. Among the GSLs, gluconapin (mean 23.11 µmole/g dry weight (DW) and glucobrassicanapin (mean 13.41 µmole/g DW) documented the most abundant compounds and contributed average 39 and 27% of the total GSLs, but indolyl and aromatic GSLs together accounted >10% of the total GSLs. The presence of significant quantities of gluconapin in the cultivars should be studied more extensively, since the GSL is mainly responsible for the bitter taste.

Anti-inflammatory and analgesic activity of ononitol monohydrate isolated from Cassia tora L. in animal models.

Ononitol monohydrate (OM) was isolated from Cassia tora L. leaves. The anti-inflammatory and analgesic activities of OM have been examined in male Wistar rats and mice. The efficacy of OM against inflammation was studied by using carrageenan-induced paw oedema, croton oil-induced ear oedema, acetic acid-induced vascular permeability, cotton pellet-induced granuloma and adjuvant-induced arthritis. The analgesic activity of OM was assessed using the acetic acid-induced abdominal constriction response, formalin-induced paw licking response and the hot-plate test. In acute type inflammation models, maximum inhibitions of 50.69 and 61.06% (P < .05) were noted with 20 mg/kg of OM in carrageenan-induced hind paw oedema and croton oil-induced ear oedema, respectively. Treatment of OM (20 mg/kg) meaningfully (P < .05) reduced the granuloma tissue formation by cotton pellet study at a rate of 36.25%. OM (20 mg/kg) inhibited 53.64% of paw thickness in adjuvant-induced arthritis model. OM has also been produced significant (P < .05) analgesic activity in acetic acid-induced abdominal constriction response, formalin-induced paw licking response and in hot-plate test suggesting its peripheral and central analgesic potential. The outcomes of the present study proposed that OM influenced on the anti-inflammatory and analgesic activities.

Protective effects of trigonelline against indomethacin-induced gastric ulcer in rats and potential underlying mechanisms.

The present study was undertaken to explore gastroprotective effects of trigonelline (TRG) and to determine the potential mechanisms involved in this action. In order to evaluate the gastroprotective efficiency of TRG, an indomethacin-induced ulcer model has been applied. Antioxidants, cytokines, adhesion markers and apoptosis levels have been analyzed for the biochemical mechanism involved in TRG activity. TRG (45 mg kg(-1)) pretreated rats significantly inhibited gastric lesions by 81.71%. Indomethacin administration raises the levels of leukotriene B4 (LTB4), lipid peroxidation and myeloperoxidase (MPO) with the significant declines of prostaglandin E2 (PGE2), superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GSH-px) levels. Conversely, TRG (45 mg kg(-1)) pretreated animals showed significant rises in PGE2 and antioxidant levels along with substantial reductions in LTB4, lipid peroxidation and MPO levels. Indomethacin-induced rats also exhibited considerable increases of pro-inflammatory cytokines including interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) levels and decreases of anti-inflammatory cytokines such as interleukin-10 (IL-10) and interleukin-4 (IL-4), but these imbalances were normalized through treatment of TRG. The protective activity of TRG against indomethacin-induced gastric ulcer has been ascribed to three important mechanisms: (1) anti-inflammatory; (2) antioxidant; (3) anti-apoptotic pathways.

Ginseng total saponin attenuates myocardial injury via anti-oxidative and anti-inflammatory properties.

BACKGROUND: Ginseng total saponin (GTS) contains various ginsenosides. These ginsenosides are widely used for treating cardiovascular diseases in Asian communities. The aim of this study was to study the effects of GTS on cardiac injury after global ischemia and reperfusion (I/R) in isolated guinea pig hearts. METHODS: Animals were subjected to normothermic ischemia for 60 minutes, followed by 120 minutes of reperfusion. GTS significantly increased aortic flow, coronary flow, and cardiac output. Moreover, GTS significantly increased left ventricular systolic pressure and the maximal rate of contraction (+dP/dt max) and relaxation (-dP/dt max). In addition, GTS has been shown to ameliorate electrocardiographic changes such as the QRS complex, QT interval, and RR interval. RESULTS: GTS significantly suppressed the biochemical parameters (i.e., lactate dehydrogenase, creatine kinase-MB fraction, and cardiac troponin I levels) and normalized the oxidative stress markers (i.e., malondialdehyde, glutathione, and nitrite). In addition, GTS also markedly inhibits the expression of interleukin-1ß (IL-1ß), IL-6, and nuclear factor-κB, and improves the expression of IL-10 in cardiac tissue. CONCLUSION: These data indicate that GTS mitigates myocardial damage by modulating the biochemical and oxidative stress related to cardiac I/R injury.

Protective effects of friedelin isolated from Azima tetracantha Lam. against ethanol-induced gastric ulcer in rats and possible underlying mechanisms.

The current study was aimed to investigate the gastroprotective effects of friedelin isolated from the hexane extract of leaves of Azima tetracantha. Ethanol-induced gastric ulcer model was used to investigate the gastroprotective effects of friedelin. Antioxidant enzymes, lipid peroxidation, nitric oxide, gastric vascular permeability, pro and anti-inflammatory cytokines and apoptosis level have been investigated. Ethanol caused severe gastric damage and friedelin pretreatment protected against its deleterious role. Antioxidant enzyme activities, anti-inflammatory cytokines, prostaglandin E2 (PGE2), constitutive nitric oxide synthase (cNOS) and mucus weight have been increased significantly. However, the vascular permeability, pro-inflammatory cytokines, inducible nitric oxide synthase (iNOS), caspase-3 and apoptosis level have significantly been decreased after friedelin ingestion. The present study has clearly demonstrated the anti-ulcer potential of friedelin, these findings suggested that friedelin could be a new useful natural gastroprotective tool against gastric ulcer.

Gastroprotective effect of nymphayol isolated from Nymphaea stellata (Willd.) flowers: contribution of antioxidant, anti-inflammatory and anti-apoptotic activities.

Gastric ulcer is an illness that affects a great number of people worldwide. The goal of the present research was to assess the anti-ulcerogenic activity of nymphayol (NYM), isolated from Nymphaea stellata, against an ethanol-induced ulcer model in rats. Administration of ethanol elevates the levels of the ulcer index (UI) along with causing tremendous increases in lipid peroxidation and myeloperoxidase (MPO) and significant decreases in gastric mucus, catalase (CAT), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), and prostaglandin E2 (PGE2). However, the NYM- (45 mg/kg) pretreated animals showed considerable increases in antioxidants, gastric mucus, and PGE2 level and significant decreases in UI, lipid peroxidation, and MPO level. Pro-inflammatory cytokines such as interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) were increased and the level of interleukin-10 (IL-10), an anti-inflammatory cytokine, was decreased in ethanol-induced ulcerated animals, and these inequalities were amended by NYM pretreatment. Pro-apoptotic markers including caspase-8, caspase-9, and caspase-3 were decreased and Bcl-2, an anti-apoptotic marker, was increased through NYM pretreatment, as compared with the ethanol-induced ulcer group. Pretreatment with indomethacin, SC560, rofecoxib, and Nω-Nitro-L-arginine methyl ester (L-NAME) considerably prevented the ulcer protective activity of NYM (45 mg/kg), indicating the involvement of cyclooxygenase (COX) and nitric oxide synthase (NOS) in NYM-mediated gastroprotection against ethanol-induced ulcer. These outcomes suggest that the gastroprotective effect of NYM might be mediated by adjustment of inflammatory mediators and apoptotic markers and increasing antioxidants.

Gastroprotective activity of violacein isolated from Chromobacterium violaceum on indomethacin-induced gastric lesions in rats: investigation of potential mechanisms of action.

Chromobacterium violaceum, Gram-negative bacteria species found in tropical regions of the world, produces a distinct deep violet-colored pigment called violacein. In the present study, we investigated whether violacein can promote a gastroprotective effect and verified the possible mechanisms involved in this action. For this study, an indomethacin-induced gastric ulcer rat model was used. The roles of biomolecules such as MPO, PGE2, pro- and anti-inflammatory cytokines, growth factors, caspase-3, NO, K(+)ATP channels, and α 2-receptors were investigated. Violacein exhibited significant gastroprotective effect against indomethacin-induced lesions, while pretreatment with L-NAME and glibenclamide (but not with NEM or yohimbine) was able to reverse this action. Pretreatment with violacein also restored cNOS level to normal and led to attenuation of enhanced apoptosis and gastric microvascular permeability. Our results suggest that violacein provides a significant gastroprotective effect in an indomethacin-induced ulcer model through the maintenance of some vital protein molecules, and this effect appears to be mediated, at least in part, by endogenous prostaglandins, NOS, K(+)ATP channel opening, and inhibition of apoptosis and gastric microvascular permeability.

Gastroprotective effect of epoxy clerodane diterpene isolated from Tinospora cordifolia Miers (Guduchi) on indomethacin-induced gastric ulcer in rats.

The present study evaluated the gastroprotective effect of epoxy clerodane diterpene (ECD), isolated from Tinospora cordifolia on indomethacin-induced gastric ulcer in rats. Administration of indomethacin exhibits extreme levels of ulcer index (UI) and myeloperoxidase (MPO) activity. Indomethacin down regulated PGE2, anti-inflammatory cytokines (IL-4, IL-10) and pro-angiogenic factors (VEGF and EGF). The ECD pretreatment considerably increased the levels of PGE2, anti-inflammatory cytokines and pro-angiogenic factors. The ulcer-healing activity of ECD was inhibited by pre-administration of the specific COX-1 inhibitor (SC560) and nonspecific NOS inhibitor (L-NAME), which indicates the involvement of PGE2 and NOS in ECD induced ulcer healing activity. These findings suggest that ECD exerts its antiulcer activity by reinforcement of defensive elements and diminishing the offensive elements.

Anti-inflammatory, analgesic and antipyretic effects of friedelin isolated from Azima tetracantha Lam. in mouse and rat models.

OBJECTIVES: Friedelin was isolated from Azima tetracantha Lam. leaves collected from Kallakurichi, Villuppuram district, Tamil Nadu, India. The anti-inflammatory, analgesic and antipyretic activities of friedelin have been investigated in Wistar rats and mice. METHODS: Friedelin was isolated from the hexane extract of leaves of A. tetracantha using column chromatography. The effects of friedelin on inflammation were studied by using carrageenan-induced hind paw oedema, croton oil-induced ear oedema, acetic acid-induced vascular permeability, cotton pellet-induced granuloma and adjuvant-induced arthritis. The analgesic effect of friedelin was evaluated using the acetic acid-induced abdominal constriction response, formalin-induced paw licking response and the hot-plate test. The antipyretic effect of friedelin was evaluated using the yeast-induced hyperthermia test in rats. KEY FINDINGS: In the acute phase of inflammation, maximum inhibitions of 52.5 and 68.7% (P<0.05) were noted with 40 mg/kg friedelin in carrageenan-induced paw oedema and croton oil-induced ear oedema, respectively. Administration of friedelin (40 mg/kg) significantly (P<0.05) decreased the formation of granuloma tissue induced by cotton pellet at a rate of 36.3%. In the adjuvant-induced arthritis test friedelin inhibited 54.5% of paw thickness. Friedelin inhibited acetic acid-induced vascular permeability in mice. Friedelin also produced significant (P<0.05) analgesic activity in the acetic acid-induced abdominal constriction response and formalin-induced paw licking response. In the hot-plate test, friedelin did not show any significant results when compared with control. Treatment with friedelin showed a significant (P<0.05) dose-dependent reduction in pyrexia in rats. CONCLUSIONS: The results suggested that friedelin possessed potent anti-inflammatory, analgesic and antipyretic activities.

Anti-diarrhoeal and ulcer-protective effects of violacein isolated from Chromobacterium violaceum in Wistar rats.

Violacein was isolated from Chromobacterium violaceum, a soil Gram-negative bacterium collected from the forest water body soil sample from Kolli Hills of Tamil Nadu, India. In the present study the anti-diarrhoeal and ulcer-protective properties of violacein were investigated in Wistar rats using castor oil, magnesium sulphate and ethanol. The intestinal transit in rats was significantly (P < 0.001) reduced and gastric emptying was delayed; 40 mg/kg of violacein elicited a greater anti-motility activity than 0.1 mg/kg of atropine. Violacein exhibited ulcer-protective properties against ethanol-induced ulceration in rats with maximal anti-ulcer activity at 40 mg/kg. Violacein also exerted significant anti-enteropooling effects, causing a dose-related inhibitory effect on castor oil-induced enteropooling in rats. A profound anti-diarrhoeal activity was observed when violacein was tested in diarrhoeic rats. The frequencies of defaecation as well as the wetness of the faecal droppings were significantly reduced. Furthermore, violacein (40 mg/kg) produced 87.84% inhibition of castor oil-induced diarrhoea in rats. The results suggested that violacein can be used for the treatment of diarrhoeal and ulcer-related diseases.