Ana Cristina Alves de Almeida

Gastroprotective and ulcer healing effects of essential oil from Hyptis spicigera Lam. (Lamiaceae)

ETHNOPHARMACOLOGICAL RELEVANCE Hyptis Jacq. (Lamiaceae) is being used in traditional medicine to treat fever, inflammation and gastric disturbances. Hyptis spicigera Lam. is a native plant distributed across the central region of Brazil. The essential oil extracted from this plant is used in folk medicine as antipyretic. AIM OF THE STUDY The effects of the essential oil obtained from the aerial parts of Hyptis spicigera (OEH) were evaluated for their gastroprotective and healing activities. MATERIALS AND METHODS OEH chemical composition was analyzed by gas chromatography-mass spectrometry (GC-MS). The gastroprotective action of the OEH was evaluated in rodent experimental models (ethanol and NSAID). To elucidate mechanisms of action, the antisecretory action and involvements of NO, SH, mucus and PGE2 were evaluated. The acetic acid-induced gastric ulcer model and Western Blot assay (COX-2 and EGF) were also used to evaluate the OEH healing capacity. RESULTS GC-MS analysis of OEH indicated three monoterpenes as major compounds: alpha-pinene (50.8%), cineole (20.3%) and beta-pinene (18.3%) and, at the dose of 100 mg/Kg, p.o., OEH provided effective gastroprotection against lesions induced by absolute ethanol (97%) and NSAID (84%) in rats. OEH do not interfere with H+ secretion in gastric mucosa and its gastric protection does not depend on nitric oxide (NO) and sulfhydryl compounds (SH). The gastroprotective action of OEH occurs due to an increase in the gastric mucus production (28%) induced by PGE2 levels. Furthermore, OEH demonstrated a great healing capacity with 87% of reduction in ulcerative lesion area. It accelerated the healing of acetic acid-induced gastric lesions due to an increase in COX-2 (75%) and EGF (115%) expression in gastric mucosa. No sign of toxicity was observed in this study, considering the analyzed parameters. CONCLUSIONS All these results suggest the efficacy and safety of Hyptis spicigera in combating and healing gastric ulcer. Considering the results, it is suggested that the OEH could probably be a good therapeutic agent for the development of new phytotherapeutic medicine for the treatment of gastric ulcer.

Mechanisms of the gastric antiulcerogenic activity of Anacardium humile St. Hil on ethanol-induced acute gastric mucosal injury in rats.

Leaves and bark infusions Anacardium humile St. Hil. (Anacardiaceae), known as in Brazil as “cajuzinho do cerrado”, have been used in folk medicine as an alternative treatment for ulcers and gastritis. This study evaluated the gastroprotective activity of an ethyl acetate extract of the leaves of A. humile (AcF) and the mechanism involved in this gastroprotection. Pretreatment concentrations (50, 100, 200 mg.kg−1) were administered by gavage. Following a 60 min. period, all the rats were orally administered 1 mL of absolute ethanol. One hour after the administration of ethanol, all groups were sacrificed, and the gastric ulcer index was calculated. Prostaglandin PGE2 concentration, gastric adherent mucous, and the participation of nitric oxide (NO) and sulfhydryl compounds in the gastroprotection process were also analyzed using the most effective tested dose (50 mg·kg−1). A histological study of the glandular stomach for the evaluation of the epithelial damage and mucus content was also performed. AcF significantly reduced the gastric damage produced by ethanol. This effect was statistically significant for the 50 mg·kg−1 group compared to control. Also, it significantly increased the PGE2 (by 10-fold) and mucous production, while pretreatment with NG-nitro-L-arginine methyl ester (L-NAME) or N-ethylmaleimide (NEM) completely abolished the gastroprotection. AcF has a protective effect against ethanol, and this effect, might be due to the augmentation of the protective mechanisms of mucosa.

Mechanisms of action underlying the gastric antiulcer activity of the Rhizophora mangle L.

ETHNOPHARMACOLOGICAL RELEVANCE Rhizophora mangle, the red mangrove, has long been known as a traditional antiulcer medicine. The present work evaluated the mechanisms of action involved in the anti-ulcer properties of the Rhizophora mangle bark extracts. MATERIALS AND METHODS Gastroprotection of Rhizophora mangle was evaluated in rodent experimental models (ethanol). To elucidate the mechanisms of action the antisecretory action and involvement of NO, SH, mucus and PGE(2) were evaluated. The acetic acid-induced gastric ulcer model, Western blotting assay (COX-1, COX-2 and EGF) and immunohistochemical localization of HSP-70, PCNA and COX-2 were also used to evaluate the Rhizophora mangle healing properties. RESULTS Results showed that Rhizophora mangle bark crude extract (CE), as well as ethyl acetate (EtOAc) and butanolic fractions (BuOH) provided significant gastroprotection at all the tested doses. Thereby, the following protocols were performed using the lowest dose capable of producing the most effective gastroprotection, which was the BuOH 0.5mg/kg (P<0.001). Several mechanisms are involved in the antiulcer activity of Rhizophora mangle, such as, participation of NO, SH and mucus. The enhancement of PGE(2) levels and the upregulation of COX-2 and EGF seem to be directly linked to the antisecretory, cytoprotective and healing effects of BuOH. HSP-70 and PCNA are also involved in this cicatrisation process. No sign of toxicity was observed in this study, considering the analyzed parameters. CONCLUSION Our study reinforces its traditional medicinal use. Considering that the current therapies are based on the use of antisecretory or cytoprotective drugs, the Rhizophora mangle arises as a promising alternative antiulcer therapy.

Antioxidant Action of Mangrove Polyphenols against Gastric Damage Induced by Absolute Ethanol and Ischemia-Reperfusion in the Rat

Rhizophora mangle, the red mangrove, has long been known as a traditional medicine. Its bark has been used as astringent, antiseptic, hemostatic, with antifungic and antiulcerogenic properties. In this paper, we aimed to evaluate the antioxidant properties of a buthanolic fraction of the R. mangle bark extract (RM) against experimental gastric ulcer in rats. Unib-Wh rats received pretreatment of R. mangle after the induction of gastric injury with absolute ethanol and ischemia-reperfusion. Gastric tissues from both methods were prepared to the enzymatic assays, the levels of sulfhydril compounds (GSH), lipid peroxides (LPO), and the activities of glutathione reductase (GR), glutathione peroxidase (GPx), superoxide dismutase (SOD) and myeloperoxidase (MPO) were measured. The RM protected the gastric mucosa in both methods used, ethanol-induced gastric ulcer and ischemia-reperfusion, probably, by modulating the activities of the enzymes SOD, GPx, and GR and increasing or maintaining the levels of GSH; in adittion, LPO levels were reduced. The results suggest that the RM antioxidant activity leads to tissue protection; thus one of the antiulcer mechanisms present on the pharmacological effects of R. mangle is the antioxidant property.

Effects of Rhizophora mangle on Experimental Colitis Induced by TNBS in Rats

Male Unib-WH rats were pretreated for two weeks with butanolic (BuOH) and ethyl acetate (EtOAc) fractions. Colitis was induced by rectal administration of TNBS, the treatment continued, and animals were sacrificed on day 7 after the TNBS administration. Phytochemical studies were performed in order to provide the characterization of the tannins present in the bark of R. mangle. Results showed that EtOAc fraction increased the levels of IL-10 (∗∗P < 0.01) and diminished the levels of TNF-α (∗∗∗P < 0.001) and IL-6 (∗∗P < 0.01). BuOH fraction reduced the MPO activity (∗∗P < 0.01) and levels of TBARS (∗∗∗P < 0.001); it also increased COX-1 expression, diminished the levels of TNF-α (∗∗∗P < 0.001), and increased the levels of IL-12 (∗∗∗P < 0.001). Besides, both treatments augmented the levels of GSH (∗P < 0.05), the activity of GSH-Px (∗∗P < 0.01 for BuOH fraction and ∗∗∗P < 0.001 for EtOAc fraction), and CAT (∗∗P < 0.01). In conclusion, both treatments ameliorated the injury induced by TNBS through different mechanisms, probably by their chemical composition which directed its activity into an antioxidant or anti-inflammatory response, leading to an immune modulation.

Abarema cochliacarpos: gastroprotective and ulcer-healing activities.

ETHNOPHARMACOLOGICAL RELEVANCE Abarema cochliacarpos (Gomes) Barneby & Grimes (Mimosaceae) is a species--in folk medicine of Lagarto city, Sergipe state, northeastern Brazil--reputed to heal gastric ulcer and gastritis. AIM OF THE STUDY Chloroform (CE) and methanolic (ME) extracts as well as ethyl acetate fraction (AF), butanolic fraction (AC) and aqueous fraction (AQF) of the methanolic extract of Abarema cochliacarpos bark were evaluated against acute gastric ulcer. The AC fraction was selected to assess its activity in ulcer healing and its gastroprotective effects via mucus and gastric secretion. MATERIAL AND METHODS The gastroprotective action of CE and ME extracts and the fractions of the latter were evaluated in a rodent experimental model. The action mechanisms, involvements of the antisecretory action and mucus production, toxicological and healing activity of the AC (150 mg/kg, p.o.) were evaluated. We also used histological analysis (HE and PAS) and immunohistochemical (PCNA, COX-2, VEGF and HSP-70) assays to evaluate the effects of Abarema cochliacarpos. RESULTS CE (200 and 400 mg/kg, p.o.) and ME (100, 200 and 400 mg/kg, p.o.) extracts were able to protect gastric mucosa against absolute ethanol. Respective inhibitions produced were: 65.31% and 83.80% by the first; 91.69%, 96.75% and 99.80% by the second; and 74.24% by the AC fraction. Antisecretory and mucus production effects were exhibited by the AC fraction, which also accelerated the healing of ulcerated gastric mucosa by stimulating proliferation factors (PCNA) and induced healing factors including COX-2, VEGF and HSP-70. CONCLUSION All these results suggest that Abarema cochliacarpos (Gomes) Barneby & Grimes presents gastroprotective effects and wound-healing properties.

Anti-inflammatory and analgesic potential of hydrolyzed extract of Agave sisalana Perrine ex Engelm., Asparagaceae

As propriedades hemolitica, anti-inflamatoria e antinociceptiva do extrato hidrolisado de Agave sisalana Perrine ex Engelm, Aparagaceae (HEAS) foram avaliadas em modelos classicos de inflamacao. Camundongos Swiss e ratos Wistars machos receberam HEAS (500 mg/kg) em duas vias de administracao p.o e i.p em solucao salina 0.9%. A hidrolise acida inibiu a acao hemolitica das saponinas atraves da retirada das cadeias laterais de acucar. O tratamento com HEAS reduziu significativamente o edema de orelha induzido por xilol em duas vias 13±1.5 e 10±0.63 mg respectivamente, p.o e i.p, em comparacao com os controles 27±1.5 salina e 13.5±1.2 AAS. O HEAS tambem diminuiu o edema induzido por carragenina 43±1.58 mg (p.o) e 17±1.26 mg (i.p), quando comparado com os grupos controle 52±1.58 (salina) e 10.05±1.58 (indometacina). HEAS apresentou efeito analgesico em modelo de contorcoes abdominais 30.7% (p.o), 88.7% (i.p) comparado com aquele produzido pelo (AAS) 70.6%. Contudo, no modelo cronico de inflamacao granuloma cotton pellet apenas a via i.p diminuiu o tecido granulomatoso (20.4±1.32 mg) comparado com os controles 30.5±2.53 (salina) e 20.2±2.18 mg (dexametasona). Esses dados sugerem que o HEAS possui atividades anti-inflamatoria e analgesica em processos agudos e cronicos.

Applications of the hexanic fraction of Agave sisalana Perrine ex Engelm (Asparagaceae): control of inflammation and pain screening

The present study evaluated the anti-inflammatory and analgesic properties of Agave sisalana Perrine in classic models of inflammation and pain. The hexanic fraction of A. sisalana (HFAS) was obtained by acid hydrolysis followed by hexanic reflux. Anti-inflammatory properties were examined in three acute mouse models (xylene ear oedema, hind paw oedema and pleurisy) and a chronic mouse model (granuloma cotton pellet). The antinociceptive potential was evaluated in chemical (acetic-acid) and thermal (tail-flick and hot-plate test) models of pain. When given orally, HFAS (5, 10, 25 and 50 mg/kg) reduced ear oedema (p < 0.0001; 52%, 71%, 62% and 42%, respectively). HFAS also reduced hind paw oedema at doses of 10 mg/kg and 25 mg/kg (p < 0.05; 42% and 58%, respectively) and pleurisy at doses of 10 mg/kg and 25 mg/kg (41% and 50%, respectively). In a chronic model, HFAS reduced inflammation by 46% and 58% at doses of 10 mg/kg and 25 mg/kg, respectively. Moreover, this fraction showed analgesic properties against the abdominal writhing in an acetic acid model (at doses of 5-25 mg/kg) with inhibitory rates of 24%, 54% and 48%. The HFAS also showed an increased latency time in the hot-plate (23% and 28%) and tail-flick tests (61% and 66%) for the 25 mg/kg and 50 mg/kg doses, respectively. These results suggest that HFAS has anti-inflammatory and analgesic properties.

Recent Trends in Pharmacological Activity of Alkaloids in Animal Colitis: Potential Use for Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is a chronic and disrupted inflammation of the gastrointestinal tract. IBD have two main conditions, Crohns disease and ulcerative colitis, and have been extensively investigated in recent years. Antibiotics derived from salicylates, steroids, immunosuppressors, and anti-TNF therapy are part of the therapeutic arsenal for IBD. However, very often patients stop responding to treatments over the time. In this context, searching for alternative agents is crucial for IBD clinical management. Natural products derived from medicinal plants are an interesting therapeutic alternative, since several studies have proven effective treatments in animal models of intestinal inflammation. Several naturally occurring compounds are potent antioxidants, both as free radical scavengers and as modulators of antioxidant enzymes expression and activity. A number of natural compounds have also been proved to inhibit the release of proinflammatory cytokines, decreasing the activation of nuclear factor κB (NF-κB), which is important to the inflammatory response in IBD. The alkaloids are substances of a very diverse class of plant secondary metabolites; an extensive list of biological activities has been attributed to alkaloids, such as being anticholinergic, antitumor, diuretic, antiviral, antihypertensive, antiulcer, analgesic, and anti-inflammatory. In the present work, studies on the pharmacological activity of alkaloids in experimental models of IBD were reviewed.

Royal Jelly and Its Dual Role in TNBS Colitis in Mice

Royal Jelly (RJ) is widely consumed in diets throughout the world due to its beneficial effects: antioxidant, antitumor and anti-inflammatory. We have investigated the role of RJ in the development of TNBS colitis in mice. Colitis was induced by a rectal instillation of TNBS at 0.1 mL per mouse. Intestine samples of the animals orally treated with RJ (100, 150, and 200 mg/kg) were collected for antioxidant assays (GSH and GSH-Px), proinflammatory protein quantification (COX-2 and NF-κB), and histological analyses. RJ 100 mg/kg maintained GSH levels and increased the activity of GSH-Px, downregulated key inflammatory mediators (COX-2 and NF-κB), and decreased the lesions caused by TNBS as shown by the histological analyses. In conclusion, RJ showed anti-inflammatory and antioxidant properties in experimental colitis, resulting in the amelioration of the macroscopic and histological analyses. These results corroborate with the RJ supplementation in diets.